Schneider-Hohendorf, Tilman; Gerdes, Lisa Ann; Pignolet, Béatrice; Gittelman, Rachel; Ostkamp, Patrick; Rubelt, Florian; Raposo, Catarina; Tackenberg, Björn; Riepenhausen, Marianne; Janoschka, Claudia; Wünsch, Christian; Bucciarelli, Florence; Flierl-Hecht, Andrea; Beltrán, Eduardo; Kümpfel, Tania; Anslinger, Katja; Gross, Catharina C; Chapman, Heidi; Kaplan, Ian; Brassat, David; Wekerle, Hartmut; Kerschensteiner, Martin; Klotz, Luisa; Lünemann, Jan D; Hohlfeld, Reinhard; Liblau, Roland; Wiendl, Heinz; Schwab, Nicholas Broader Epstein-Barr virus-specific T cell receptor repertoire in patients with multiple sclerosis Journal Article In: J Exp Med, vol. 219, no. 11, 2022, ISSN: 1540-9538. @article{pmid36048016,
title = {Broader Epstein-Barr virus-specific T cell receptor repertoire in patients with multiple sclerosis},
author = {Tilman Schneider-Hohendorf and Lisa Ann Gerdes and Béatrice Pignolet and Rachel Gittelman and Patrick Ostkamp and Florian Rubelt and Catarina Raposo and Björn Tackenberg and Marianne Riepenhausen and Claudia Janoschka and Christian Wünsch and Florence Bucciarelli and Andrea Flierl-Hecht and Eduardo Beltrán and Tania Kümpfel and Katja Anslinger and Catharina C Gross and Heidi Chapman and Ian Kaplan and David Brassat and Hartmut Wekerle and Martin Kerschensteiner and Luisa Klotz and Jan D Lünemann and Reinhard Hohlfeld and Roland Liblau and Heinz Wiendl and Nicholas Schwab},
doi = {10.1084/jem.20220650},
issn = {1540-9538},
year = {2022},
date = {2022-11-01},
urldate = {2022-11-01},
journal = {J Exp Med},
volume = {219},
number = {11},
abstract = {Epstein-Barr virus (EBV) infection precedes multiple sclerosis (MS) pathology and cross-reactive antibodies might link EBV infection to CNS autoimmunity. As an altered anti-EBV T cell reaction was suggested in MS, we queried peripheral blood T cell receptor β chain (TCRβ) repertoires of 1,395 MS patients, 887 controls, and 35 monozygotic, MS-discordant twin pairs for multimer-confirmed, viral antigen-specific TCRβ sequences. We detected more MHC-I-restricted EBV-specific TCRβ sequences in MS patients. Differences in genetics or upbringing could be excluded by validation in monozygotic twin pairs discordant for MS. Anti-VLA-4 treatment amplified this observation, while interferon β- or anti-CD20 treatment did not modulate EBV-specific T cell occurrence. In healthy individuals, EBV-specific CD8+ T cells were of an effector-memory phenotype in peripheral blood and cerebrospinal fluid. In MS patients, cerebrospinal fluid also contained EBV-specific central-memory CD8+ T cells, suggesting recent priming. Therefore, MS is not only preceded by EBV infection, but also associated with broader EBV-specific TCR repertoires, consistent with an ongoing anti-EBV immune reaction in MS.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Epstein-Barr virus (EBV) infection precedes multiple sclerosis (MS) pathology and cross-reactive antibodies might link EBV infection to CNS autoimmunity. As an altered anti-EBV T cell reaction was suggested in MS, we queried peripheral blood T cell receptor β chain (TCRβ) repertoires of 1,395 MS patients, 887 controls, and 35 monozygotic, MS-discordant twin pairs for multimer-confirmed, viral antigen-specific TCRβ sequences. We detected more MHC-I-restricted EBV-specific TCRβ sequences in MS patients. Differences in genetics or upbringing could be excluded by validation in monozygotic twin pairs discordant for MS. Anti-VLA-4 treatment amplified this observation, while interferon β- or anti-CD20 treatment did not modulate EBV-specific T cell occurrence. In healthy individuals, EBV-specific CD8+ T cells were of an effector-memory phenotype in peripheral blood and cerebrospinal fluid. In MS patients, cerebrospinal fluid also contained EBV-specific central-memory CD8+ T cells, suggesting recent priming. Therefore, MS is not only preceded by EBV infection, but also associated with broader EBV-specific TCR repertoires, consistent with an ongoing anti-EBV immune reaction in MS. |
Tarbouriech, Nicolas; Chenavier, Florian; Kawasaki, Junna; Bachiri, Kamel; Bourhis, Jean-Marie; Legrand, Pierre; Freslon, Lily L.; Laurent, Estelle M. N.; Suberbielle, Elsa; Ruigrok, Rob W. H.; Tomonaga, Keizo; Gonzalez-Dunia, Daniel; Horie, Masayuki; Coyaud, Etienne; Crépin, Thibaut Borna Disease Virus 1 Phosphoprotein Forms a Tetramer and Interacts with Host Factors Involved in DNA Double-Strand Break Repair and mRNA Processing Journal Article In: Viruses, vol. 14, no. 11, 2022, ISSN: 1999-4915. @article{Tarbouriech2022,
title = {Borna Disease Virus 1 Phosphoprotein Forms a Tetramer and Interacts with Host Factors Involved in DNA Double-Strand Break Repair and mRNA Processing},
author = {Nicolas Tarbouriech and Florian Chenavier and Junna Kawasaki and Kamel Bachiri and Jean-Marie Bourhis and Pierre Legrand and Lily L. Freslon and Estelle M. N. Laurent and Elsa Suberbielle and Rob W. H. Ruigrok and Keizo Tomonaga and Daniel Gonzalez-Dunia and Masayuki Horie and Etienne Coyaud and Thibaut Crépin},
doi = {10.3390/v14112358},
issn = {1999-4915},
year = {2022},
date = {2022-11-00},
urldate = {2022-11-00},
journal = {Viruses},
volume = {14},
number = {11},
publisher = {MDPI AG},
abstract = {<jats:p>Determining the structural organisation of viral replication complexes and unravelling the impact of infection on cellular homeostasis represent important challenges in virology. This may prove particularly useful when confronted with viruses that pose a significant threat to human health, that appear unique within their family, or for which knowledge is scarce. Among Mononegavirales, bornaviruses (family Bornaviridae) stand out due to their compact genomes and their nuclear localisation for replication. The recent recognition of the zoonotic potential of several orthobornaviruses has sparked a surge of interest in improving our knowledge on this viral family. In this work, we provide a complete analysis of the structural organisation of Borna disease virus 1 (BoDV-1) phosphoprotein (P), an important cofactor for polymerase activity. Using X-ray diffusion and diffraction experiments, we revealed that BoDV-1 P adopts a long coiled-coil α-helical structure split into two parts by an original β-strand twist motif, which is highly conserved across the members of whole Orthobornavirus genus and may regulate viral replication. In parallel, we used BioID to determine the proximal interactome of P in living cells. We confirmed previously known interactors and identified novel proteins linked to several biological processes such as DNA repair or mRNA metabolism. Altogether, our study provides important structure/function cues, which may improve our understanding of BoDV-1 pathogenesis.</jats:p>},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
<jats:p>Determining the structural organisation of viral replication complexes and unravelling the impact of infection on cellular homeostasis represent important challenges in virology. This may prove particularly useful when confronted with viruses that pose a significant threat to human health, that appear unique within their family, or for which knowledge is scarce. Among Mononegavirales, bornaviruses (family Bornaviridae) stand out due to their compact genomes and their nuclear localisation for replication. The recent recognition of the zoonotic potential of several orthobornaviruses has sparked a surge of interest in improving our knowledge on this viral family. In this work, we provide a complete analysis of the structural organisation of Borna disease virus 1 (BoDV-1) phosphoprotein (P), an important cofactor for polymerase activity. Using X-ray diffusion and diffraction experiments, we revealed that BoDV-1 P adopts a long coiled-coil α-helical structure split into two parts by an original β-strand twist motif, which is highly conserved across the members of whole Orthobornavirus genus and may regulate viral replication. In parallel, we used BioID to determine the proximal interactome of P in living cells. We confirmed previously known interactors and identified novel proteins linked to several biological processes such as DNA repair or mRNA metabolism. Altogether, our study provides important structure/function cues, which may improve our understanding of BoDV-1 pathogenesis.</jats:p> |
Maurel S Petitfils C, Payros G Identification of bacterial lipopeptides as key players in IBS Journal Article In: Gut, 2022. @article{C2022,
title = {Identification of bacterial lipopeptides as key players in IBS},
author = {Petitfils C, Maurel S, Payros G, Hueber A, Agaiz B, Gazzo G, Marrocco R, Auvray F, Langevin G, Motta JP, Floch P, Tremblay-Franco M, Galano JM, Guy A, Durand T, Lachambre S, Durbec A, Hussein H, Decraecker L, Bertrand-Michel J, Saoudi A, Oswald E, Poisbeau P, Dietrich G, Melchior C, Boeckxstaens G, Serino M, Le Faouder P, Cenac N.},
url = {https://pubmed.ncbi.nlm.nih.gov/36241390/},
doi = {10.1136/gutjnl-2022-328084},
year = {2022},
date = {2022-10-14},
journal = {Gut},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
|
Martin-Blondel, Guillaume; Marcelin, Anne-Genevieve; Soulié, Cathia; Kaisaridi, Sofia; Lusivika-Nzinga, Clovis; Dorival, Céline; Nailler, Laura; Boston, Anaïs; Melenotte, Cléa; Cabié, André; Choquet, Christophe; Coustillères, François; Martellosio, Jean-Philippe; Gaube, Géraldine; Trinh-Duc, Albert; Ronchetti, Anne-Marie; Pourcher, Valerie; Chauveau, Marie; Lacombe, Karine; Peiffer-Smadja, Nathan; Housset, Pierre; Perrot, Aurore; Pialoux, Gilles; Martin, Aurélie; Dubee, Vincent; Devaux, Mathilde; Frey, Jérôme; Cazanave, Charles; Liblau, Roland; Carrat, Fabrice; Yordanov, Youri Sotrovimab to prevent severe COVID-19 in high-risk patients infected with Omicron BA.2 Miscellaneous 2022, ISSN: 1532-2742. @misc{pmid35803386,
title = {Sotrovimab to prevent severe COVID-19 in high-risk patients infected with Omicron BA.2},
author = {Guillaume Martin-Blondel and Anne-Genevieve Marcelin and Cathia Soulié and Sofia Kaisaridi and Clovis Lusivika-Nzinga and Céline Dorival and Laura Nailler and Anaïs Boston and Cléa Melenotte and André Cabié and Christophe Choquet and François Coustillères and Jean-Philippe Martellosio and Géraldine Gaube and Albert Trinh-Duc and Anne-Marie Ronchetti and Valerie Pourcher and Marie Chauveau and Karine Lacombe and Nathan Peiffer-Smadja and Pierre Housset and Aurore Perrot and Gilles Pialoux and Aurélie Martin and Vincent Dubee and Mathilde Devaux and Jérôme Frey and Charles Cazanave and Roland Liblau and Fabrice Carrat and Youri Yordanov},
doi = {10.1016/j.jinf.2022.06.033},
issn = {1532-2742},
year = {2022},
date = {2022-10-01},
urldate = {2022-10-01},
journal = {J Infect},
volume = {85},
number = {4},
pages = {e104--e108},
keywords = {},
pubstate = {published},
tppubtype = {misc}
}
|
B, Todorova; O, Godon; E, Conde; CM, Gillis; B, Iannascoli; O, Richard-Le Goff; D, Fiole; LT, Roumenina; JHW, Leusen; AJ, Murphy; LE, Macdonald; LL, Reber; F, Jönsson; P, Bruhns IgG Subclass-Dependent Pulmonary Antigen Retention during Acute IgG-Dependent Systemic Anaphylaxis in Mice. Journal Article In: J Immunol, 2022. @article{36165182,
title = {IgG Subclass-Dependent Pulmonary Antigen Retention during Acute IgG-Dependent Systemic Anaphylaxis in Mice.},
author = {Todorova B and Godon O and Conde E and Gillis CM and Iannascoli B and Richard-Le Goff O and Fiole D and Roumenina LT and Leusen JHW and Murphy AJ and Macdonald LE and Reber LL and Jönsson F and Bruhns P},
url = {https://pubmed.ncbi.nlm.nih.gov/36165182/},
doi = {10.4049/jimmunol.2200234},
year = {2022},
date = {2022-10-01},
journal = {J Immunol},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
|
Apert, Cécile; Galindo-Albarrán, Ariel; Castan, Sarah; Detraves, Claire; Michaud, Héloise; McJannett, Nicola; Haegeman, Bart; Fillatreau, Simon; Malissen, Bernard; Hollander, Georg; Zuklys, Saulius; Santamaria, Jérémy; Joffre, Olivier; Romagnoli, Paola; van Meerwijk, Joost IL-2 and IL-15 drive intrathymic development of distinct periphery-seeding CD4+Foxp3+ regulatory T lymphocytes Journal Article In: Frontiers in Immunology, 2022. @article{vanJoost.2022,
title = {IL-2 and IL-15 drive intrathymic development of distinct periphery-seeding CD4+Foxp3+ regulatory T lymphocytes},
author = {Cécile Apert and Ariel Galindo-Albarrán and Sarah Castan and Claire Detraves and Héloise Michaud and Nicola McJannett and Bart Haegeman and Simon Fillatreau and Bernard Malissen and Georg Hollander and Saulius Zuklys and Jérémy Santamaria and Olivier Joffre and Paola Romagnoli and Joost van Meerwijk},
url = {https://www.frontiersin.org/articles/10.3389/fimmu.2022.965303/full},
doi = {10.3389/fimmu.2022.965303},
year = {2022},
date = {2022-09-08},
journal = {Frontiers in Immunology},
abstract = {Development of Foxp3-expressing regulatory T-lymphocytes (Treg) in the thymus is controlled by signals delivered in T-cell precursors via the TCR, co-stimulatory receptors, and cytokine receptors. In absence of IL-2, IL-15 or their receptors, fewer Treg apparently develop in the thymus. However, it was recently shown that a substantial part of thymic Treg are cells that had recirculated from the periphery back to the thymus, troubling interpretation of these results. We therefore reassessed the involvement of IL-2 and IL-15 in the development of Treg, taking into account Treg-recirculation. At the age of three weeks, when in wt and IL-15-deficient (but not in IL-2-deficient) mice substantial amounts of recirculating Treg are present in the thymus, we found similarly reduced proportions of newly developed Treg in absence of IL-2 or IL-15, and in absence of both cytokines even less Treg developed. In neonates, when practically no recirculating Treg were found in the thymus, the absence of IL-2 led to substantially more reduced Treg-development than deficiency in IL-15. IL-2 but not IL-15 modulated the CD25, GITR, OX40, and CD73-phenotypes of the thymus-egress-competent and periphery-seeding Treg-population. Interestingly, IL-2 and IL-15 also modulated the TCR-repertoire expressed by developing Treg. Upon transfer into Treg-less Foxp3sf mice, newly developed Treg from IL-2- (and to a much lesser extent IL-15-) deficient mice suppressed immunopathology less efficiently than wt Treg. Taken together, our results firmly establish important non-redundant quantitative and qualitative roles for IL-2 and, to a lesser extent, IL-15 in intrathymic Treg-development.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Development of Foxp3-expressing regulatory T-lymphocytes (Treg) in the thymus is controlled by signals delivered in T-cell precursors via the TCR, co-stimulatory receptors, and cytokine receptors. In absence of IL-2, IL-15 or their receptors, fewer Treg apparently develop in the thymus. However, it was recently shown that a substantial part of thymic Treg are cells that had recirculated from the periphery back to the thymus, troubling interpretation of these results. We therefore reassessed the involvement of IL-2 and IL-15 in the development of Treg, taking into account Treg-recirculation. At the age of three weeks, when in wt and IL-15-deficient (but not in IL-2-deficient) mice substantial amounts of recirculating Treg are present in the thymus, we found similarly reduced proportions of newly developed Treg in absence of IL-2 or IL-15, and in absence of both cytokines even less Treg developed. In neonates, when practically no recirculating Treg were found in the thymus, the absence of IL-2 led to substantially more reduced Treg-development than deficiency in IL-15. IL-2 but not IL-15 modulated the CD25, GITR, OX40, and CD73-phenotypes of the thymus-egress-competent and periphery-seeding Treg-population. Interestingly, IL-2 and IL-15 also modulated the TCR-repertoire expressed by developing Treg. Upon transfer into Treg-less Foxp3sf mice, newly developed Treg from IL-2- (and to a much lesser extent IL-15-) deficient mice suppressed immunopathology less efficiently than wt Treg. Taken together, our results firmly establish important non-redundant quantitative and qualitative roles for IL-2 and, to a lesser extent, IL-15 in intrathymic Treg-development. |
Bergamelli, Mathilde; Martin, Hélène; Aubert, Yann; Mansuy, Jean-Michel; Marcellin, Marlène; Burlet-Schiltz, Odile; Hurbain, Ilse; Raposo, Graça; Izopet, Jacques; Fournier, Thierry; Benchoua, Alexandra; Bénard, Mélinda; Groussolles, Marion; Cartron, Géraldine; Gac, Yann Tanguy Le; Moinard, Nathalie; D’Angelo, Gisela; Malnou, Cécile E. Human Cytomegalovirus Modifies Placental Small Extracellular Vesicle Composition to Enhance Infection of Fetal Neural Cells In Vitro Journal Article In: Viruses, vol. 14, no. 9, 2022, ISSN: 1999-4915. @article{Bergamelli2022,
title = {Human Cytomegalovirus Modifies Placental Small Extracellular Vesicle Composition to Enhance Infection of Fetal Neural Cells In Vitro},
author = {Mathilde Bergamelli and Hélène Martin and Yann Aubert and Jean-Michel Mansuy and Marlène Marcellin and Odile Burlet-Schiltz and Ilse Hurbain and Graça Raposo and Jacques Izopet and Thierry Fournier and Alexandra Benchoua and Mélinda Bénard and Marion Groussolles and Géraldine Cartron and Yann Tanguy Le Gac and Nathalie Moinard and Gisela D’Angelo and Cécile E. Malnou},
doi = {10.3390/v14092030},
issn = {1999-4915},
year = {2022},
date = {2022-09-00},
urldate = {2022-09-00},
journal = {Viruses},
volume = {14},
number = {9},
publisher = {MDPI AG},
abstract = {<jats:p>Although placental small extracellular vesicles (sEVs) are extensively studied in the context of pregnancy, little is known about their role during viral congenital infection, especially at the beginning of pregnancy. In this study, we examined the consequences of human cytomegalovirus (hCMV) infection on sEVs production, composition, and function using an immortalized human cytotrophoblast cell line derived from first trimester placenta. By combining complementary approaches of biochemistry, electron microscopy, and quantitative proteomic analysis, we showed that hCMV infection increases the yield of sEVs produced by cytotrophoblasts and modifies their protein content towards a potential proviral phenotype. We further demonstrate that sEVs secreted by hCMV-infected cytotrophoblasts potentiate infection in naive recipient cells of fetal origin, including human neural stem cells. Importantly, these functional consequences are also observed with sEVs prepared from an ex vivo model of infected histocultures from early placenta. Based on these findings, we propose that placental sEVs could be important actors favoring viral dissemination to the fetal brain during hCMV congenital infection.</jats:p>},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
<jats:p>Although placental small extracellular vesicles (sEVs) are extensively studied in the context of pregnancy, little is known about their role during viral congenital infection, especially at the beginning of pregnancy. In this study, we examined the consequences of human cytomegalovirus (hCMV) infection on sEVs production, composition, and function using an immortalized human cytotrophoblast cell line derived from first trimester placenta. By combining complementary approaches of biochemistry, electron microscopy, and quantitative proteomic analysis, we showed that hCMV infection increases the yield of sEVs produced by cytotrophoblasts and modifies their protein content towards a potential proviral phenotype. We further demonstrate that sEVs secreted by hCMV-infected cytotrophoblasts potentiate infection in naive recipient cells of fetal origin, including human neural stem cells. Importantly, these functional consequences are also observed with sEVs prepared from an ex vivo model of infected histocultures from early placenta. Based on these findings, we propose that placental sEVs could be important actors favoring viral dissemination to the fetal brain during hCMV congenital infection.</jats:p> |
Merkler, Doron; Vincenti, Ilena; Masson, Frederick; Liblau, Roland S Tissue-resident CD8 T cells in central nervous system inflammatory diseases: present at the crime scene and …guilty Journal Article In: Curr Opin Immunol, vol. 77, pp. 102211, 2022, ISSN: 1879-0372. @article{pmid35644112,
title = {Tissue-resident CD8 T cells in central nervous system inflammatory diseases: present at the crime scene and …guilty},
author = {Doron Merkler and Ilena Vincenti and Frederick Masson and Roland S Liblau},
doi = {10.1016/j.coi.2022.102211},
issn = {1879-0372},
year = {2022},
date = {2022-08-01},
urldate = {2022-08-01},
journal = {Curr Opin Immunol},
volume = {77},
pages = {102211},
abstract = {Tissue-resident memory T cells (T) represent a subset of antigen-experienced T cells that are constantly retained in a given tissue with limited trafficking through the circulation. These cells are characterized by expression of molecules enabling their tissue anchoring and downregulation of molecules promoting tissue egress. They reside at sites of previous antigen encounter and their number increases with age. T have been shown to provide rapid and efficient protection against tissue reinfection and T density correlates with efficient antitumor responses. Intriguingly, the density of CD8 T is increased in the central nervous system (CNS) of patients with neuroinflammatory diseases such as multiple sclerosis, or suffering from neurodegenerative diseases. In this review, we discuss current knowledge regarding the diversity of CNS-resident CD8 T cells and their role in CNS autoimmunity. Given their likely contribution to the protracted course of several inflammatory diseases of the CNS, their therapeutic targeting becomes an important challenge.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Tissue-resident memory T cells (T) represent a subset of antigen-experienced T cells that are constantly retained in a given tissue with limited trafficking through the circulation. These cells are characterized by expression of molecules enabling their tissue anchoring and downregulation of molecules promoting tissue egress. They reside at sites of previous antigen encounter and their number increases with age. T have been shown to provide rapid and efficient protection against tissue reinfection and T density correlates with efficient antitumor responses. Intriguingly, the density of CD8 T is increased in the central nervous system (CNS) of patients with neuroinflammatory diseases such as multiple sclerosis, or suffering from neurodegenerative diseases. In this review, we discuss current knowledge regarding the diversity of CNS-resident CD8 T cells and their role in CNS autoimmunity. Given their likely contribution to the protracted course of several inflammatory diseases of the CNS, their therapeutic targeting becomes an important challenge. |
Chiu, Isaac M; Liblau, Roland Editorial overview: Special section neuroimmunology: Neuroimmune interactions in health and disease Miscellaneous 2022, ISSN: 1879-0372. @misc{pmid35792467,
title = {Editorial overview: Special section neuroimmunology: Neuroimmune interactions in health and disease},
author = {Isaac M Chiu and Roland Liblau},
doi = {10.1016/j.coi.2022.102232},
issn = {1879-0372},
year = {2022},
date = {2022-08-01},
urldate = {2022-08-01},
journal = {Curr Opin Immunol},
volume = {77},
pages = {102232},
keywords = {},
pubstate = {published},
tppubtype = {misc}
}
|
Martin, Hélène; Barthelemy, Jonathan; Chin, Yamileth; Bergamelli, Mathilde; Moinard, Nathalie; Cartron, Géraldine; Gac, Yann Tanguy Le; Malnou, Cécile E.; Simonin, Yannick Usutu Virus Infects Human Placental Explants and Induces Congenital Defects in Mice Journal Article In: Viruses, vol. 14, no. 8, 2022, ISSN: 1999-4915. @article{Martin2022b,
title = {Usutu Virus Infects Human Placental Explants and Induces Congenital Defects in Mice},
author = {Hélène Martin and Jonathan Barthelemy and Yamileth Chin and Mathilde Bergamelli and Nathalie Moinard and Géraldine Cartron and Yann Tanguy Le Gac and Cécile E. Malnou and Yannick Simonin},
doi = {10.3390/v14081619},
issn = {1999-4915},
year = {2022},
date = {2022-08-00},
urldate = {2022-08-00},
journal = {Viruses},
volume = {14},
number = {8},
publisher = {MDPI AG},
abstract = {<jats:p>Usutu virus (USUV) is a neurotropic mosquito-borne flavivirus that has dispersed quickly in Europe these past years. This arbovirus mainly follows an enzootic cycle involving mosquitoes and birds, but can also infect other mammals, causing notably sporadic cases in humans. Although it is mainly asymptomatic or responsible for mild clinical symptoms, USUV has been associated with neurological disorders, such as encephalitis and meningoencephalitis, highlighting the potential health threat of this virus. Among the different transmission routes described for other flaviviruses, the capacity for some of them to be transmitted vertically has been demonstrated, notably for Zika virus or West Nile virus, which are closely related to USUV. To evaluate the ability of USUV to replicate in the placenta and gain access to the fetus, we combined the use of several trophoblast model cell lines, ex vivo human placental explant cultures from first and third trimester of pregnancy, and in vivo USUV-infected pregnant mice. Our data demonstrate that human placental cells and tissues are permissive to USUV replication, and suggest that viral transmission can occur in mice during gestation. Hence, our observations suggest that USUV could be efficiently transmitted by the vertical route.</jats:p>},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
<jats:p>Usutu virus (USUV) is a neurotropic mosquito-borne flavivirus that has dispersed quickly in Europe these past years. This arbovirus mainly follows an enzootic cycle involving mosquitoes and birds, but can also infect other mammals, causing notably sporadic cases in humans. Although it is mainly asymptomatic or responsible for mild clinical symptoms, USUV has been associated with neurological disorders, such as encephalitis and meningoencephalitis, highlighting the potential health threat of this virus. Among the different transmission routes described for other flaviviruses, the capacity for some of them to be transmitted vertically has been demonstrated, notably for Zika virus or West Nile virus, which are closely related to USUV. To evaluate the ability of USUV to replicate in the placenta and gain access to the fetus, we combined the use of several trophoblast model cell lines, ex vivo human placental explant cultures from first and third trimester of pregnancy, and in vivo USUV-infected pregnant mice. Our data demonstrate that human placental cells and tissues are permissive to USUV replication, and suggest that viral transmission can occur in mice during gestation. Hence, our observations suggest that USUV could be efficiently transmitted by the vertical route.</jats:p> |
Quelle est la réalité des infections humaines par les Bornavirus ? Journal Article In: Virologie, vol. 26, no. 4, pp. 275–281, 2022, ISSN: 1267-8694. @article{2022,
title = {Quelle est la réalité des infections humaines par les Bornavirus ?},
doi = {10.1684/vir.2022.0965},
issn = {1267-8694},
year = {2022},
date = {2022-07-01},
urldate = {2022-07-01},
journal = {Virologie},
volume = {26},
number = {4},
pages = {275--281},
publisher = {John Libbey Eurotext},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
|
Bernard-Valnet, Raphaël; Frieser, David; Nguyen, Xuan Hung; Khajavi, Leila; Quériault, Clémence; Arthaud, Sébastien; Melzi, Silvia; Fusade-Boyer, Maxime; Masson, Frederick; Zytnicki, Matthias; Saoudi, Abdelhadi; Dauvilliers, Yves; Peyron, Christelle; Bauer, Jan; Liblau, Roland S Influenza vaccination induces autoimmunity against orexinergic neurons in a mouse model for narcolepsy Journal Article In: Brain, vol. 145, no. 6, pp. 2018–2030, 2022, ISSN: 1460-2156. @article{pmid35552381b,
title = {Influenza vaccination induces autoimmunity against orexinergic neurons in a mouse model for narcolepsy},
author = {Raphaël Bernard-Valnet and David Frieser and Xuan Hung Nguyen and Leila Khajavi and Clémence Quériault and Sébastien Arthaud and Silvia Melzi and Maxime Fusade-Boyer and Frederick Masson and Matthias Zytnicki and Abdelhadi Saoudi and Yves Dauvilliers and Christelle Peyron and Jan Bauer and Roland S Liblau},
doi = {10.1093/brain/awab455},
issn = {1460-2156},
year = {2022},
date = {2022-06-01},
urldate = {2022-06-01},
journal = {Brain},
volume = {145},
number = {6},
pages = {2018--2030},
abstract = {Narcolepsy with cataplexy or narcolepsy type 1 is a disabling chronic sleep disorder resulting from the destruction of orexinergic neurons in the hypothalamus. The tight association of narcolepsy with HLA-DQB1*06:02 strongly suggest an autoimmune origin to this disease. Furthermore, converging epidemiological studies have identified an increased incidence for narcolepsy in Europe following Pandemrix® vaccination against the 2009-2010 pandemic 'influenza' virus strain. The potential immunological link between the Pandemrix® vaccination and narcolepsy remains, however, unknown. Deciphering these mechanisms may reveal pathways potentially at play in most cases of narcolepsy. Here, we developed a mouse model allowing to track and study the T-cell response against 'influenza' virus haemagglutinin, which was selectively expressed in the orexinergic neurons as a new self-antigen. Pandemrix® vaccination in this mouse model resulted in hypothalamic inflammation and selective destruction of orexin-producing neurons. Further investigations on the relative contribution of T-cell subsets in this process revealed that haemagglutinin-specific CD4 T cells were necessary for the development of hypothalamic inflammation, but insufficient for killing orexinergic neurons. Conversely, haemagglutinin-specific CD8 T cells could not initiate inflammation but were the effectors of the destruction of orexinergic neurons. Additional studies revealed pathways potentially involved in the disease process. Notably, the interferon-γ pathway was proven essential, as interferon-γ-deficient CD8 T cells were unable to elicit the loss of orexinergic neurons. Our work demonstrates that an immunopathological process mimicking narcolepsy can be elicited by immune cross-reactivity between a vaccine antigen and a neuronal self-antigen. This process relies on a synergy between autoreactive CD4 and CD8 T cells for disease development. This work furthers our understanding of the mechanisms and pathways potentially involved in the development of a neurological side effect due to a vaccine and, likely, to narcolepsy in general.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Narcolepsy with cataplexy or narcolepsy type 1 is a disabling chronic sleep disorder resulting from the destruction of orexinergic neurons in the hypothalamus. The tight association of narcolepsy with HLA-DQB1*06:02 strongly suggest an autoimmune origin to this disease. Furthermore, converging epidemiological studies have identified an increased incidence for narcolepsy in Europe following Pandemrix® vaccination against the 2009-2010 pandemic 'influenza' virus strain. The potential immunological link between the Pandemrix® vaccination and narcolepsy remains, however, unknown. Deciphering these mechanisms may reveal pathways potentially at play in most cases of narcolepsy. Here, we developed a mouse model allowing to track and study the T-cell response against 'influenza' virus haemagglutinin, which was selectively expressed in the orexinergic neurons as a new self-antigen. Pandemrix® vaccination in this mouse model resulted in hypothalamic inflammation and selective destruction of orexin-producing neurons. Further investigations on the relative contribution of T-cell subsets in this process revealed that haemagglutinin-specific CD4 T cells were necessary for the development of hypothalamic inflammation, but insufficient for killing orexinergic neurons. Conversely, haemagglutinin-specific CD8 T cells could not initiate inflammation but were the effectors of the destruction of orexinergic neurons. Additional studies revealed pathways potentially involved in the disease process. Notably, the interferon-γ pathway was proven essential, as interferon-γ-deficient CD8 T cells were unable to elicit the loss of orexinergic neurons. Our work demonstrates that an immunopathological process mimicking narcolepsy can be elicited by immune cross-reactivity between a vaccine antigen and a neuronal self-antigen. This process relies on a synergy between autoreactive CD4 and CD8 T cells for disease development. This work furthers our understanding of the mechanisms and pathways potentially involved in the development of a neurological side effect due to a vaccine and, likely, to narcolepsy in general. |
Bernard-Valnet, Raphaël; Frieser, David; Nguyen, Xuan Hung; Khajavi, Leila; Quériault, Clémence; Arthaud, Sébastien; Melzi, Silvia; Fusade-Boyer, Maxime; Masson, Frederick; Zytnicki, Matthias; Saoudi, Abdelhadi; Dauvilliers, Yves; Peyron, Christelle; Bauer, Jan; Liblau, Roland S Influenza vaccination induces autoimmunity against orexinergic neurons in a mouse model for narcolepsy Journal Article In: Brain, vol. 145, no. 6, pp. 2018–2030, 2022, ISSN: 1460-2156. @article{pmid35552381,
title = {Influenza vaccination induces autoimmunity against orexinergic neurons in a mouse model for narcolepsy},
author = {Raphaël Bernard-Valnet and David Frieser and Xuan Hung Nguyen and Leila Khajavi and Clémence Quériault and Sébastien Arthaud and Silvia Melzi and Maxime Fusade-Boyer and Frederick Masson and Matthias Zytnicki and Abdelhadi Saoudi and Yves Dauvilliers and Christelle Peyron and Jan Bauer and Roland S Liblau},
doi = {10.1093/brain/awab455},
issn = {1460-2156},
year = {2022},
date = {2022-06-01},
urldate = {2022-06-01},
journal = {Brain},
volume = {145},
number = {6},
pages = {2018--2030},
abstract = {Narcolepsy with cataplexy or narcolepsy type 1 is a disabling chronic sleep disorder resulting from the destruction of orexinergic neurons in the hypothalamus. The tight association of narcolepsy with HLA-DQB1*06:02 strongly suggest an autoimmune origin to this disease. Furthermore, converging epidemiological studies have identified an increased incidence for narcolepsy in Europe following Pandemrix® vaccination against the 2009-2010 pandemic 'influenza' virus strain. The potential immunological link between the Pandemrix® vaccination and narcolepsy remains, however, unknown. Deciphering these mechanisms may reveal pathways potentially at play in most cases of narcolepsy. Here, we developed a mouse model allowing to track and study the T-cell response against 'influenza' virus haemagglutinin, which was selectively expressed in the orexinergic neurons as a new self-antigen. Pandemrix® vaccination in this mouse model resulted in hypothalamic inflammation and selective destruction of orexin-producing neurons. Further investigations on the relative contribution of T-cell subsets in this process revealed that haemagglutinin-specific CD4 T cells were necessary for the development of hypothalamic inflammation, but insufficient for killing orexinergic neurons. Conversely, haemagglutinin-specific CD8 T cells could not initiate inflammation but were the effectors of the destruction of orexinergic neurons. Additional studies revealed pathways potentially involved in the disease process. Notably, the interferon-γ pathway was proven essential, as interferon-γ-deficient CD8 T cells were unable to elicit the loss of orexinergic neurons. Our work demonstrates that an immunopathological process mimicking narcolepsy can be elicited by immune cross-reactivity between a vaccine antigen and a neuronal self-antigen. This process relies on a synergy between autoreactive CD4 and CD8 T cells for disease development. This work furthers our understanding of the mechanisms and pathways potentially involved in the development of a neurological side effect due to a vaccine and, likely, to narcolepsy in general.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Narcolepsy with cataplexy or narcolepsy type 1 is a disabling chronic sleep disorder resulting from the destruction of orexinergic neurons in the hypothalamus. The tight association of narcolepsy with HLA-DQB1*06:02 strongly suggest an autoimmune origin to this disease. Furthermore, converging epidemiological studies have identified an increased incidence for narcolepsy in Europe following Pandemrix® vaccination against the 2009-2010 pandemic 'influenza' virus strain. The potential immunological link between the Pandemrix® vaccination and narcolepsy remains, however, unknown. Deciphering these mechanisms may reveal pathways potentially at play in most cases of narcolepsy. Here, we developed a mouse model allowing to track and study the T-cell response against 'influenza' virus haemagglutinin, which was selectively expressed in the orexinergic neurons as a new self-antigen. Pandemrix® vaccination in this mouse model resulted in hypothalamic inflammation and selective destruction of orexin-producing neurons. Further investigations on the relative contribution of T-cell subsets in this process revealed that haemagglutinin-specific CD4 T cells were necessary for the development of hypothalamic inflammation, but insufficient for killing orexinergic neurons. Conversely, haemagglutinin-specific CD8 T cells could not initiate inflammation but were the effectors of the destruction of orexinergic neurons. Additional studies revealed pathways potentially involved in the disease process. Notably, the interferon-γ pathway was proven essential, as interferon-γ-deficient CD8 T cells were unable to elicit the loss of orexinergic neurons. Our work demonstrates that an immunopathological process mimicking narcolepsy can be elicited by immune cross-reactivity between a vaccine antigen and a neuronal self-antigen. This process relies on a synergy between autoreactive CD4 and CD8 T cells for disease development. This work furthers our understanding of the mechanisms and pathways potentially involved in the development of a neurological side effect due to a vaccine and, likely, to narcolepsy in general. |
Kamphuis JBJ Worrall WPM, Stackowicz J The anti-FcεRI antibody MAR-1 depletes basophils and cross-reacts with myeloid cells through its Fc portion Journal Article In: Allergy, vol. 77, no. 6, pp. 1903-1906, 2022. @article{WPM2022,
title = {The anti-FcεRI antibody MAR-1 depletes basophils and cross-reacts with myeloid cells through its Fc portion},
author = {Worrall WPM, Kamphuis JBJ, Stackowicz J, Mougel A, Mauré E, Pecalvel C, Brûlé S, Bruhns P, Guilleminault L, Reber LL.},
url = {https://pubmed.ncbi.nlm.nih.gov/35244223/},
doi = { 10.1111/all.15269},
year = {2022},
date = {2022-06-01},
journal = {Allergy},
volume = {77},
number = {6},
pages = {1903-1906},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
|
Nicolas Gaudenzio, Lilian Basso Mast cell-neuron axis in allergy Journal Article In: Curr Opin Immunol ., vol. 77, no. 102213, pp. 1-6, 2022. @article{Gaudenzio2022,
title = {Mast cell-neuron axis in allergy},
author = {Nicolas Gaudenzio, Lilian Basso},
year = {2022},
date = {2022-05-20},
journal = {Curr Opin Immunol .},
volume = {77},
number = {102213},
pages = {1-6},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
|
Gaudenzio N, Liblau RS. Immune cells impede repair of old neurons Journal Article In: Science, vol. 376, no. 6594, pp. 694-695, 2022. @article{N2022,
title = {Immune cells impede repair of old neurons},
author = {Gaudenzio N, Liblau RS.},
editor = {{Lambert de Rouvroit}, Catherine},
year = {2022},
date = {2022-05-13},
journal = {Science},
volume = {376},
number = {6594},
pages = { 694-695},
abstract = {The regenerative capacity of older people is reduced, resulting in decreased tissue function and resilience. Accordingly, the regeneration of the sciatic nerve after injury has been reported to be less efficient and slower in older people (1). One of the hallmarks of aging is altered intercellular communication, which is often accompanied by increased density of immune cells within tissues and excessive release of proinflammatory mediators, called inflammaging (2, 3). In this context, the immune system disturbs tissue homeostasis and impedes functional recovery. However, the precise mechanisms underlying this pathophysiological process are largely elusive, which is a barrier to rational treatment design. On page 715 of this issue, Zhou et al. (4) describe a mechanism by which aged sensory neurons release the chemoattractive protein C-X-C motif chemokine ligand 13 (CXCL13). Upon sciatic nerve injury in aged, but not young, mice, this results in the recruitment of CD8+ T cells that prevent axonal regeneration.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
The regenerative capacity of older people is reduced, resulting in decreased tissue function and resilience. Accordingly, the regeneration of the sciatic nerve after injury has been reported to be less efficient and slower in older people (1). One of the hallmarks of aging is altered intercellular communication, which is often accompanied by increased density of immune cells within tissues and excessive release of proinflammatory mediators, called inflammaging (2, 3). In this context, the immune system disturbs tissue homeostasis and impedes functional recovery. However, the precise mechanisms underlying this pathophysiological process are largely elusive, which is a barrier to rational treatment design. On page 715 of this issue, Zhou et al. (4) describe a mechanism by which aged sensory neurons release the chemoattractive protein C-X-C motif chemokine ligand 13 (CXCL13). Upon sciatic nerve injury in aged, but not young, mice, this results in the recruitment of CD8+ T cells that prevent axonal regeneration. |
Gaudenzio, Nicolas; Liblau, Roland S Immune cells impede repair of old neurons Journal Article In: Science, vol. 376, no. 6594, pp. 694–695, 2022, ISSN: 1095-9203. @article{pmid35549427,
title = {Immune cells impede repair of old neurons},
author = {Nicolas Gaudenzio and Roland S Liblau},
doi = {10.1126/science.abp9878},
issn = {1095-9203},
year = {2022},
date = {2022-05-01},
urldate = {2022-05-01},
journal = {Science},
volume = {376},
number = {6594},
pages = {694--695},
abstract = {Interfering with age-related neuroimmune interactions promotes nerve regeneration.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Interfering with age-related neuroimmune interactions promotes nerve regeneration. |
JBJ, Kamphuis; LL, Reber; H, Eutamène; V, Theodorou Increased fermentable carbohydrate intake alters colonic mucus barrier function through glycation processes and increased mast cell counts. Journal Article In: FASEB J, 2022. @article{35394686,
title = {Increased fermentable carbohydrate intake alters colonic mucus barrier function through glycation processes and increased mast cell counts.},
author = {Kamphuis JBJ and Reber LL and Eutamène H and Theodorou V},
url = {https://pubmed.ncbi.nlm.nih.gov/35394686/},
doi = {10.1096/fj.202100494RRR},
year = {2022},
date = {2022-05-01},
journal = {FASEB J},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
|
Hohlfeld, Reinhard; Liblau, Roland S Toward identification of personalized immunological profiles in multiple sclerosis Journal Article In: Sci Adv, vol. 8, no. 17, pp. eabq4849, 2022, ISSN: 2375-2548. @article{pmid35476442,
title = {Toward identification of personalized immunological profiles in multiple sclerosis},
author = {Reinhard Hohlfeld and Roland S Liblau},
doi = {10.1126/sciadv.abq4849},
issn = {2375-2548},
year = {2022},
date = {2022-04-01},
urldate = {2022-04-01},
journal = {Sci Adv},
volume = {8},
number = {17},
pages = {eabq4849},
abstract = {The diversity of four previously unidentified autoantigens found in multiple sclerosis mirrors its notorious clinical variability.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
The diversity of four previously unidentified autoantigens found in multiple sclerosis mirrors its notorious clinical variability. |
Frieser, David; Pignata, Aurora; Khajavi, Leila; Shlesinger, Danielle; Gonzalez-Fierro, Carmen; Nguyen, Xuan-Hung; Yermanos, Alexander; Merkler, Doron; Höftberger, Romana; Desestret, Virginie; Mair, Katharina M; Bauer, Jan; Masson, Frederick; Liblau, Roland S Tissue-resident CD8 T cells drive compartmentalized and chronic autoimmune damage against CNS neurons Journal Article In: Sci Transl Med, vol. 14, no. 640, pp. eabl6157, 2022, ISSN: 1946-6242. @article{pmid35417189,
title = {Tissue-resident CD8 T cells drive compartmentalized and chronic autoimmune damage against CNS neurons},
author = {David Frieser and Aurora Pignata and Leila Khajavi and Danielle Shlesinger and Carmen Gonzalez-Fierro and Xuan-Hung Nguyen and Alexander Yermanos and Doron Merkler and Romana Höftberger and Virginie Desestret and Katharina M Mair and Jan Bauer and Frederick Masson and Roland S Liblau},
doi = {10.1126/scitranslmed.abl6157},
issn = {1946-6242},
year = {2022},
date = {2022-04-01},
urldate = {2022-04-01},
journal = {Sci Transl Med},
volume = {14},
number = {640},
pages = {eabl6157},
abstract = {The mechanisms underlying the chronicity of autoimmune diseases of the central nervous system (CNS) are largely unknown. In particular, it is unclear whether tissue-resident memory T cells (T) contribute to lesion pathogenesis during chronic CNS autoimmunity. Here, we observed that a high frequency of brain-infiltrating CD8 T cells exhibit a T-like phenotype in human autoimmune encephalitis. Using mouse models of neuronal autoimmunity and a combination of T single-cell transcriptomics, high-dimensional flow cytometry, and histopathology, we found that pathogenic CD8 T cells behind the blood-brain barrier adopt a characteristic T differentiation program, and we revealed their phenotypic and functional heterogeneity. In the diseased CNS, autoreactive tissue-resident CD8 T cells sustained focal neuroinflammation and progressive loss of neurons, independently of recirculating CD8 T cells. Consistently, a large fraction of autoreactive tissue-resident CD8 T cells exhibited proliferative potential as well as proinflammatory and cytotoxic properties. Persistence of tissue-resident CD8 T cells in the CNS and their functional output, but not their initial differentiation, were crucially dependent on CD4 T cells. Collectively, our results point to tissue-resident CD8 T cells as essential drivers of chronic CNS autoimmunity and suggest that therapies targeting this compartmentalized autoreactive T cell subset might be effective for treating CNS autoimmune diseases.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
The mechanisms underlying the chronicity of autoimmune diseases of the central nervous system (CNS) are largely unknown. In particular, it is unclear whether tissue-resident memory T cells (T) contribute to lesion pathogenesis during chronic CNS autoimmunity. Here, we observed that a high frequency of brain-infiltrating CD8 T cells exhibit a T-like phenotype in human autoimmune encephalitis. Using mouse models of neuronal autoimmunity and a combination of T single-cell transcriptomics, high-dimensional flow cytometry, and histopathology, we found that pathogenic CD8 T cells behind the blood-brain barrier adopt a characteristic T differentiation program, and we revealed their phenotypic and functional heterogeneity. In the diseased CNS, autoreactive tissue-resident CD8 T cells sustained focal neuroinflammation and progressive loss of neurons, independently of recirculating CD8 T cells. Consistently, a large fraction of autoreactive tissue-resident CD8 T cells exhibited proliferative potential as well as proinflammatory and cytotoxic properties. Persistence of tissue-resident CD8 T cells in the CNS and their functional output, but not their initial differentiation, were crucially dependent on CD4 T cells. Collectively, our results point to tissue-resident CD8 T cells as essential drivers of chronic CNS autoimmunity and suggest that therapies targeting this compartmentalized autoreactive T cell subset might be effective for treating CNS autoimmune diseases. |