2025
|
Morelli, María Paula; Martin, Candela; Pellegrini, Joaquín Miguel; Blanco, Federico; Bigi, Fabiana; Ciallella, Lorena; Musella, Rosa; Mieres, Adriana Rodriguez; de Casado, Graciela C; Palmero, Domingo Juan; García, Verónica Edith Neutrophils from tuberculosis patients are polarized toward pro-inflammatory and anti-inflammatory phenotypes according to the disease severity Article de journal Dans: J Immunol, vol. 214, no. 6, p. 1173–1186, 2025, ISSN: 1550-6606. @article{pmid40184042,
title = {Neutrophils from tuberculosis patients are polarized toward pro-inflammatory and anti-inflammatory phenotypes according to the disease severity},
author = {María Paula Morelli and Candela Martin and Joaquín Miguel Pellegrini and Federico Blanco and Fabiana Bigi and Lorena Ciallella and Rosa Musella and Adriana Rodriguez Mieres and Graciela C de Casado and Domingo Juan Palmero and Verónica Edith García},
doi = {10.1093/jimmun/vkaf010},
issn = {1550-6606},
year = {2025},
date = {2025-06-01},
urldate = {2025-06-01},
journal = {J Immunol},
volume = {214},
number = {6},
pages = {1173--1186},
abstract = {Neutrophils are the first line of defense against pathogens, combating them by using several antimicrobial mechanisms. These cells display a remarkable plasticity that can be molded by the different environments that neutrophils confront to protect the host, therefore presenting diverse phenotypes. Actually, pro- and anti-inflammatory neutrophils populations (N1- and N2-like phenotypes) have been described in cancer and inflammatory disorders. However, the identification of N1/N2 neutrophil subtypes in human intracellular bacterial diseases remains unexplored. Here, we characterized neutrophils from tuberculosis (TB) patients presenting distinct immunological status according to their disease severity. TB patients were classified as high or low responders (HR or LR) in accordance with their immunity against Mycobacterium tuberculosis (Mtb). Interestingly, by analyzing the phenotypic and functional characteristics of neutrophils from the two groups of TB patients we demonstrated that HR patient's neutrophils display a pro-inflammatory N1-like phenotype, whereas LR patient's neutrophils show an anti-inflammatory N2-like phenotype. Remarkably, whereas neutrophils from both groups of patients phagocytized MtbH37Rv strain equally, HR TB's neutrophils displayed a significantly increased ability to kill pathogenic Mtb as compared to neutrophils from LR TB patients that presented a diminished capacity of bacterial elimination. Together, our findings suggest the existence of different subtypes of neutrophils in TB patients according to their immune response to Mtb and disease severity, indicating that neutrophils might be promising targets for TB host-directed therapy.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Neutrophils are the first line of defense against pathogens, combating them by using several antimicrobial mechanisms. These cells display a remarkable plasticity that can be molded by the different environments that neutrophils confront to protect the host, therefore presenting diverse phenotypes. Actually, pro- and anti-inflammatory neutrophils populations (N1- and N2-like phenotypes) have been described in cancer and inflammatory disorders. However, the identification of N1/N2 neutrophil subtypes in human intracellular bacterial diseases remains unexplored. Here, we characterized neutrophils from tuberculosis (TB) patients presenting distinct immunological status according to their disease severity. TB patients were classified as high or low responders (HR or LR) in accordance with their immunity against Mycobacterium tuberculosis (Mtb). Interestingly, by analyzing the phenotypic and functional characteristics of neutrophils from the two groups of TB patients we demonstrated that HR patient's neutrophils display a pro-inflammatory N1-like phenotype, whereas LR patient's neutrophils show an anti-inflammatory N2-like phenotype. Remarkably, whereas neutrophils from both groups of patients phagocytized MtbH37Rv strain equally, HR TB's neutrophils displayed a significantly increased ability to kill pathogenic Mtb as compared to neutrophils from LR TB patients that presented a diminished capacity of bacterial elimination. Together, our findings suggest the existence of different subtypes of neutrophils in TB patients according to their immune response to Mtb and disease severity, indicating that neutrophils might be promising targets for TB host-directed therapy. |
Pellegrini, Joaquín Miguel; Keriel, Anne; Gorvel, Laurent; Hanniffy, Sean; Arce-Gorvel, Vilma; Bosilkovski, Mile; Solera, Javier; Méresse, Stéphane; Mémet, Sylvie; Gorvel, Jean-Pierre SLAMF7 and SLAMF8 receptors shape human plasmacytoid dendritic cell responses to intracellular bacteria Article de journal Dans: J Clin Invest, vol. 135, no. 8, 2025, ISSN: 1558-8238. @article{pmid40231463,
title = {SLAMF7 and SLAMF8 receptors shape human plasmacytoid dendritic cell responses to intracellular bacteria},
author = {Joaquín Miguel Pellegrini and Anne Keriel and Laurent Gorvel and Sean Hanniffy and Vilma Arce-Gorvel and Mile Bosilkovski and Javier Solera and Stéphane Méresse and Sylvie Mémet and Jean-Pierre Gorvel},
doi = {10.1172/JCI182467},
issn = {1558-8238},
year = {2025},
date = {2025-04-01},
urldate = {2025-04-01},
journal = {J Clin Invest},
volume = {135},
number = {8},
abstract = {Plasmacytoid dendritic cells (pDCs), professional type I IFN-producing cells, have been implicated in host responses against bacterial infections. However, their role in host defense is debated, and the operating molecular mechanisms are unknown. Certain signaling lymphocyte activation molecule family (SLAMF) members act as microbial sensors and modulate immune functions in response to infection. Here, human blood transcriptomic analyses reveal the involvement of SLAMF7 and SLAMF8 in many infectious diseases, with elevated levels associated with type I IFN responses in salmonellosis and brucellosis patients. We further identify SLAMF7 and SLAMF8 as key regulators of human pDC function. They activate pDC maturation and cytokine production during infection with bacteria that induce acute (Salmonella) or chronic (Brucella) inflammation. SLAMF7 and SLAMF8 signal through NF-κB, IRF7, and STAT-1, and limit mitochondrial ROS accumulation upon Salmonella infection. Remarkably, this SLAMF7/8-dependent control of mitochondrial ROS levels favors bacterial persistence and NF-κB activation. Overall, our results unravel essential shared multifaceted roles of SLAMF7 and SLAMF8 in finely tuning human pDC responses to intracellular bacterial infections with potential for future diagnostic and therapeutic applications.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Plasmacytoid dendritic cells (pDCs), professional type I IFN-producing cells, have been implicated in host responses against bacterial infections. However, their role in host defense is debated, and the operating molecular mechanisms are unknown. Certain signaling lymphocyte activation molecule family (SLAMF) members act as microbial sensors and modulate immune functions in response to infection. Here, human blood transcriptomic analyses reveal the involvement of SLAMF7 and SLAMF8 in many infectious diseases, with elevated levels associated with type I IFN responses in salmonellosis and brucellosis patients. We further identify SLAMF7 and SLAMF8 as key regulators of human pDC function. They activate pDC maturation and cytokine production during infection with bacteria that induce acute (Salmonella) or chronic (Brucella) inflammation. SLAMF7 and SLAMF8 signal through NF-κB, IRF7, and STAT-1, and limit mitochondrial ROS accumulation upon Salmonella infection. Remarkably, this SLAMF7/8-dependent control of mitochondrial ROS levels favors bacterial persistence and NF-κB activation. Overall, our results unravel essential shared multifaceted roles of SLAMF7 and SLAMF8 in finely tuning human pDC responses to intracellular bacterial infections with potential for future diagnostic and therapeutic applications. |
Niu, Hua; Herb, Marc; Pellegrini, Joaquin Miguel Editorial: The role of autophagy in infectious diseases, volume II Divers 2025, ISSN: 2235-2988. @misc{pmid41561090,
title = {Editorial: The role of autophagy in infectious diseases, volume II},
author = {Hua Niu and Marc Herb and Joaquin Miguel Pellegrini},
doi = {10.3389/fcimb.2025.1764139},
issn = {2235-2988},
year = {2025},
date = {2025-01-01},
urldate = {2025-01-01},
journal = {Front Cell Infect Microbiol},
volume = {15},
pages = {1764139},
keywords = {},
pubstate = {published},
tppubtype = {misc}
}
|
Pellegrini, Joaquin M; González-Espinoza, Gabriela; Shayan, Raheleh R; Hysenaj, Lisiena; Rouma, Thomas; Arce-Gorvel, Vilma; Lelouard, Hugues; Popoff, Dimitri; Zhao, Yun; Hanniffy, Sean; Castillo-Zeledón, Amanda; Loperena-Barber, Maite; Celis-Gutierrez, Javier; Mionnet, Cyrille; Bosilkovski, Mile; Solera, Javier; Muraille, Eric; Barquero-Calvo, Elías; Moreno, Edgardo; Conde-Álvarez, Raquel; Moriyón, Ignacio; Gorvel, Jean-Pierre; Mémet, Sylvie Brucella abortus impairs T lymphocyte responsiveness by mobilizing IL-1RA-secreting omental neutrophils Article de journal Dans: Nat Commun, vol. 16, no. 1, p. 862, 2025, ISSN: 2041-1723. @article{pmid39833171,
title = {Brucella abortus impairs T lymphocyte responsiveness by mobilizing IL-1RA-secreting omental neutrophils},
author = {Joaquin M Pellegrini and Gabriela González-Espinoza and Raheleh R Shayan and Lisiena Hysenaj and Thomas Rouma and Vilma Arce-Gorvel and Hugues Lelouard and Dimitri Popoff and Yun Zhao and Sean Hanniffy and Amanda Castillo-Zeledón and Maite Loperena-Barber and Javier Celis-Gutierrez and Cyrille Mionnet and Mile Bosilkovski and Javier Solera and Eric Muraille and Elías Barquero-Calvo and Edgardo Moreno and Raquel Conde-Álvarez and Ignacio Moriyón and Jean-Pierre Gorvel and Sylvie Mémet},
doi = {10.1038/s41467-024-55799-2},
issn = {2041-1723},
year = {2025},
date = {2025-01-01},
urldate = {2025-01-01},
journal = {Nat Commun},
volume = {16},
number = {1},
pages = {862},
abstract = {Immune evasion strategies of Brucella, the etiologic agent of brucellosis, a global zoonosis, remain partially understood. The omentum, a tertiary lymphoid organ part of visceral adipose tissue, has never been explored as a Brucella reservoir. We report that B. abortus infects and replicates within murine omental macrophages. Throughout the chronic phase of infection, the omentum accumulates macrophages, monocytes and neutrophils. The maintenance of PD-L1Sca-1 macrophages, monocytes and neutrophils in the omentum depends on the wadC-encoded determinant of Brucella LPS. We demonstrate that PD-L1Sca-1 murine omental neutrophils produce high levels of IL-1RA leading to T cell hyporesponsiveness. These findings corroborate brucellosis patient analysis of whole blood displaying upregulation of PDL1 and Ly6E genes, and of serum exhibiting high levels of IL-1RA. Overall, the omentum, a reservoir for B. abortus, promotes bacterial persistence and causes CD4 and CD8 T cell immunosuppression by IL-1RA secreted by PD-L1Sca-1 neutrophils.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Immune evasion strategies of Brucella, the etiologic agent of brucellosis, a global zoonosis, remain partially understood. The omentum, a tertiary lymphoid organ part of visceral adipose tissue, has never been explored as a Brucella reservoir. We report that B. abortus infects and replicates within murine omental macrophages. Throughout the chronic phase of infection, the omentum accumulates macrophages, monocytes and neutrophils. The maintenance of PD-L1Sca-1 macrophages, monocytes and neutrophils in the omentum depends on the wadC-encoded determinant of Brucella LPS. We demonstrate that PD-L1Sca-1 murine omental neutrophils produce high levels of IL-1RA leading to T cell hyporesponsiveness. These findings corroborate brucellosis patient analysis of whole blood displaying upregulation of PDL1 and Ly6E genes, and of serum exhibiting high levels of IL-1RA. Overall, the omentum, a reservoir for B. abortus, promotes bacterial persistence and causes CD4 and CD8 T cell immunosuppression by IL-1RA secreted by PD-L1Sca-1 neutrophils. |
2024
|
Loperena-Barber, Maite; Elizalde-Bielsa, Aitor; Salvador-Bescós, Miriam; Ruiz-Rodríguez, Paula; Pellegrini, Joaquin Miguel; Renau-Mínguez, Chantal; Lancaster, Rebecca; Zúñiga-Ripa, Amaia; Iriarte, Maite; Bengoechea, Jose A; Coscollá, Mireia; Gorvel, Jean-Pierre; Moriyón, Ignacio; Conde-Álvarez, Raquel Article de journal Dans: Infect Genet Evol, vol. 123, p. 105625, 2024, ISSN: 1567-7257. @article{pmid38906517,
author = {Maite Loperena-Barber and Aitor Elizalde-Bielsa and Miriam Salvador-Bescós and Paula Ruiz-Rodríguez and Joaquin Miguel Pellegrini and Chantal Renau-Mínguez and Rebecca Lancaster and Amaia Zúñiga-Ripa and Maite Iriarte and Jose A Bengoechea and Mireia Coscollá and Jean-Pierre Gorvel and Ignacio Moriyón and Raquel Conde-Álvarez},
doi = {10.1016/j.meegid.2024.105625},
issn = {1567-7257},
year = {2024},
date = {2024-09-01},
urldate = {2024-09-01},
journal = {Infect Genet Evol},
volume = {123},
pages = {105625},
abstract = {The genus Pseudochrobactrum encompasses free-living bacteria phylogenetically close to Ochrobactrum opportunistic pathogens and to Brucella, facultative intracellular parasites causing brucellosis, a worldwide-extended and grave zoonosis. Recently, Pseudochrobactrum strains were isolated from Brucella natural hosts on Brucella selective media, potentially causing diagnostic confusions. Strikingly, P. algeriensis was isolated from cattle lymph nodes, organs that are inimical to bacteria. Here, we analyse P. algeriensis potential virulence factors in comparison with Ochrobactrum and Brucella. Consistent with genomic analyses, Western-Blot analyses confirmed that P. algeriensis lacks the ability to synthesize the N-formylperosamine O-polysaccharide characteristic of the lipopolysaccharide (LPS) of smooth Brucella core species. However, unlike other Pseudochrobactrum but similar to some early diverging brucellae, P. algeriensis carries genes potentially synthetizing a rhamnose-based O-polysaccharide LPS. Lipid A analysis by MALDI-TOF demonstrated that P. algeriensis LPS bears a lipid A with a reduced pathogen-associated molecular pattern, a trait shared with Ochrobactrum and Brucella that is essential to generate a highly stable outer membrane and to delay immune activation. Also, although not able to multiply intracellularly in macrophages, the analysis of P. algeriensis cell lipid envelope revealed the presence of large amounts of cationic aminolipids, which may account for the extremely high resistance of P. algeriensis to bactericidal peptides and could favor colonization of mucosae and transient survival in Brucella hosts. However, two traits critical in Brucella pathogenicity are either significantly different (T4SS [VirB]) or absent (erythritol catabolic pathway) in P. algeriensis. This work shows that, while diverging in other characteristics, lipidic envelope features relevant in Brucella pathogenicity are conserved in Brucellaceae. The constant presence of these features strongly suggests that reinforcement of the envelope integrity as an adaptive advantage in soil was maintained in Brucella because of the similarity of some environmental challenges, such as the action of cationic peptide antibiotics and host defense peptides. This information adds knowledge about the evolution of Brucellaceae, and also underlines the taxonomical differences of the three genera compared.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
The genus Pseudochrobactrum encompasses free-living bacteria phylogenetically close to Ochrobactrum opportunistic pathogens and to Brucella, facultative intracellular parasites causing brucellosis, a worldwide-extended and grave zoonosis. Recently, Pseudochrobactrum strains were isolated from Brucella natural hosts on Brucella selective media, potentially causing diagnostic confusions. Strikingly, P. algeriensis was isolated from cattle lymph nodes, organs that are inimical to bacteria. Here, we analyse P. algeriensis potential virulence factors in comparison with Ochrobactrum and Brucella. Consistent with genomic analyses, Western-Blot analyses confirmed that P. algeriensis lacks the ability to synthesize the N-formylperosamine O-polysaccharide characteristic of the lipopolysaccharide (LPS) of smooth Brucella core species. However, unlike other Pseudochrobactrum but similar to some early diverging brucellae, P. algeriensis carries genes potentially synthetizing a rhamnose-based O-polysaccharide LPS. Lipid A analysis by MALDI-TOF demonstrated that P. algeriensis LPS bears a lipid A with a reduced pathogen-associated molecular pattern, a trait shared with Ochrobactrum and Brucella that is essential to generate a highly stable outer membrane and to delay immune activation. Also, although not able to multiply intracellularly in macrophages, the analysis of P. algeriensis cell lipid envelope revealed the presence of large amounts of cationic aminolipids, which may account for the extremely high resistance of P. algeriensis to bactericidal peptides and could favor colonization of mucosae and transient survival in Brucella hosts. However, two traits critical in Brucella pathogenicity are either significantly different (T4SS [VirB]) or absent (erythritol catabolic pathway) in P. algeriensis. This work shows that, while diverging in other characteristics, lipidic envelope features relevant in Brucella pathogenicity are conserved in Brucellaceae. The constant presence of these features strongly suggests that reinforcement of the envelope integrity as an adaptive advantage in soil was maintained in Brucella because of the similarity of some environmental challenges, such as the action of cationic peptide antibiotics and host defense peptides. This information adds knowledge about the evolution of Brucellaceae, and also underlines the taxonomical differences of the three genera compared. |
2023
|
Tateosian, Nancy Liliana; Morelli, María Paula; Pellegrini, Joaquín Miguel; García, Verónica Edith Beyond the Clinic: The Activation of Diverse Cellular and Humoral Factors Shapes the Immunological Status of Patients with Active Tuberculosis Article de journal Dans: Int J Mol Sci, vol. 24, no. 5, 2023, ISSN: 1422-0067. @article{pmid36902461,
title = {Beyond the Clinic: The Activation of Diverse Cellular and Humoral Factors Shapes the Immunological Status of Patients with Active Tuberculosis},
author = {Nancy Liliana Tateosian and María Paula Morelli and Joaquín Miguel Pellegrini and Verónica Edith García},
doi = {10.3390/ijms24055033},
issn = {1422-0067},
year = {2023},
date = {2023-03-01},
urldate = {2023-03-01},
journal = {Int J Mol Sci},
volume = {24},
number = {5},
abstract = { (), the etiologic agent of tuberculosis (TB), has killed nearly one billion people in the last two centuries. Nowadays, TB remains a major global health problem, ranking among the thirteen leading causes of death worldwide. Human TB infection spans different levels of stages: incipient, subclinical, latent and active TB, all of them with varying symptoms, microbiological characteristics, immune responses and pathologies profiles. After infection, interacts with diverse cells of both innate and adaptive immune compartments, playing a crucial role in the modulation and development of the pathology. Underlying TB clinical manifestations, individual immunological profiles can be identified in patients with active TB according to the strength of their immune responses to Mtb infection, defining diverse endotypes. Those different endotypes are regulated by a complex interaction of the patient's cellular metabolism, genetic background, epigenetics, and gene transcriptional regulation. Here, we review immunological categorizations of TB patients based on the activation of different cellular populations (both myeloid and lymphocytic subsets) and humoral mediators (such as cytokines and lipid mediators). The analysis of the participating factors that operate during active infection shaping the immunological status or immune endotypes of TB patients could contribute to the development of Host Directed Therapy.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
(), the etiologic agent of tuberculosis (TB), has killed nearly one billion people in the last two centuries. Nowadays, TB remains a major global health problem, ranking among the thirteen leading causes of death worldwide. Human TB infection spans different levels of stages: incipient, subclinical, latent and active TB, all of them with varying symptoms, microbiological characteristics, immune responses and pathologies profiles. After infection, interacts with diverse cells of both innate and adaptive immune compartments, playing a crucial role in the modulation and development of the pathology. Underlying TB clinical manifestations, individual immunological profiles can be identified in patients with active TB according to the strength of their immune responses to Mtb infection, defining diverse endotypes. Those different endotypes are regulated by a complex interaction of the patient's cellular metabolism, genetic background, epigenetics, and gene transcriptional regulation. Here, we review immunological categorizations of TB patients based on the activation of different cellular populations (both myeloid and lymphocytic subsets) and humoral mediators (such as cytokines and lipid mediators). The analysis of the participating factors that operate during active infection shaping the immunological status or immune endotypes of TB patients could contribute to the development of Host Directed Therapy. |
Pellegrini, Joaquin Miguel; Morelli, María Paula; Colombo, María Isabel; García, Verónica Edith Editorial: Beneficial and detrimental host cellular responses against infection Divers 2023, ISSN: 2235-2988. @misc{pmid38089813,
title = {Editorial: Beneficial and detrimental host cellular responses against infection},
author = {Joaquin Miguel Pellegrini and María Paula Morelli and María Isabel Colombo and Verónica Edith García},
doi = {10.3389/fcimb.2023.1332084},
issn = {2235-2988},
year = {2023},
date = {2023-01-01},
urldate = {2023-01-01},
journal = {Front Cell Infect Microbiol},
volume = {13},
pages = {1332084},
keywords = {},
pubstate = {published},
tppubtype = {misc}
}
|
2022
|
Pellegrini, Joaquin Miguel; Gorvel, Jean-Pierre; Mémet, Sylvie Immunosuppressive Mechanisms in Brucellosis in Light of Chronic Bacterial Diseases Article de journal Dans: Microorganisms, vol. 10, no. 7, 2022, ISSN: 2076-2607. @article{pmid35888979,
title = {Immunosuppressive Mechanisms in Brucellosis in Light of Chronic Bacterial Diseases},
author = {Joaquin Miguel Pellegrini and Jean-Pierre Gorvel and Sylvie Mémet},
doi = {10.3390/microorganisms10071260},
issn = {2076-2607},
year = {2022},
date = {2022-06-01},
urldate = {2022-06-01},
journal = {Microorganisms},
volume = {10},
number = {7},
abstract = {Brucellosis is considered one of the major zoonoses worldwide, constituting a critical livestock and human health concern with a huge socio-economic burden. genus, its etiologic agent, is composed of intracellular bacteria that have evolved a prodigious ability to elude and shape host immunity to establish chronic infection. 's intracellular lifestyle and pathogen-associated molecular patterns, such as its specific lipopolysaccharide (LPS), are key factors for hiding and hampering recognition by the immune system. Here, we will review the current knowledge of evading and immunosuppressive mechanisms elicited by species to persist stealthily in their hosts, such as those triggered by their LPS and cyclic β-1,2-d-glucan or involved in neutrophil and monocyte avoidance, antigen presentation impairment, the modulation of T cell responses and immunometabolism. Attractive strategies exploited by other successful chronic pathogenic bacteria, including , , and , will be also discussed, with a special emphasis on the mechanisms operating in brucellosis, such as granuloma formation, pyroptosis, and manipulation of type I and III IFNs, B cells, innate lymphoid cells, and host lipids. A better understanding of these stratagems is essential to fighting bacterial chronic infections and designing innovative treatments and vaccines.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Brucellosis is considered one of the major zoonoses worldwide, constituting a critical livestock and human health concern with a huge socio-economic burden. genus, its etiologic agent, is composed of intracellular bacteria that have evolved a prodigious ability to elude and shape host immunity to establish chronic infection. 's intracellular lifestyle and pathogen-associated molecular patterns, such as its specific lipopolysaccharide (LPS), are key factors for hiding and hampering recognition by the immune system. Here, we will review the current knowledge of evading and immunosuppressive mechanisms elicited by species to persist stealthily in their hosts, such as those triggered by their LPS and cyclic β-1,2-d-glucan or involved in neutrophil and monocyte avoidance, antigen presentation impairment, the modulation of T cell responses and immunometabolism. Attractive strategies exploited by other successful chronic pathogenic bacteria, including , , and , will be also discussed, with a special emphasis on the mechanisms operating in brucellosis, such as granuloma formation, pyroptosis, and manipulation of type I and III IFNs, B cells, innate lymphoid cells, and host lipids. A better understanding of these stratagems is essential to fighting bacterial chronic infections and designing innovative treatments and vaccines. |
Amiano, Nicolás O; Pellegrini, Joaquín M; Morelli, María P; Martinena, Camila; Rolandelli, Agustín; Castello, Florencia A; Casco, Nicolás; Ciallella, Lorena M; de Casado, Graciela C; Armitano, Rita; Stupka, Juan; Gallego, Claudio; Palmero, Domingo J; García, Verónica E; Tateosian, Nancy L Circulating Monocyte-Like Myeloid Derived Suppressor Cells and CD16 Positive Monocytes Correlate With Immunological Responsiveness of Tuberculosis Patients Article de journal Dans: Front Cell Infect Microbiol, vol. 12, p. 841741, 2022, ISSN: 2235-2988. @article{pmid35360105,
title = {Circulating Monocyte-Like Myeloid Derived Suppressor Cells and CD16 Positive Monocytes Correlate With Immunological Responsiveness of Tuberculosis Patients},
author = {Nicolás O Amiano and Joaquín M Pellegrini and María P Morelli and Camila Martinena and Agustín Rolandelli and Florencia A Castello and Nicolás Casco and Lorena M Ciallella and Graciela C de Casado and Rita Armitano and Juan Stupka and Claudio Gallego and Domingo J Palmero and Verónica E García and Nancy L Tateosian},
doi = {10.3389/fcimb.2022.841741},
issn = {2235-2988},
year = {2022},
date = {2022-01-01},
urldate = {2022-01-01},
journal = {Front Cell Infect Microbiol},
volume = {12},
pages = {841741},
abstract = {Alterations of myeloid cell populations have been reported in patients with tuberculosis (TB). In this work, we studied the relationship between myeloid-derived suppressor cells (MDSC) and monocytes subsets with the immunological responsiveness of TB patients. Individuals with active TB were classified as low responders (LR-TB) or high responders (HR-TB) according to their T cell responses against a cell lysate of (-Ag). Thus, LR-TB, individuals with severe disease, display a weaker immune response to compare to HR-TB, subjects with strong immunity against the bacteria. We observed that LR-TB presented higher percentages of CD16 positive monocytes as compared to HR-TB and healthy donors. Moreover, monocyte-like (M-MDSC) and polymorphonuclear-like (PMN-MDSC) MDSC were increased in patients and the proportion of M-MDSC inversely correlated with IFN-γ levels released after -Ag stimulation in HR-TB. We also found that LR-TB displayed the highest percentages of circulating M-MDSC. These results demonstrate that CD16 positive monocytes and M-MDSC frequencies could be used as another immunological classification parameter. Interestingly, in LR-TB, frequencies of CD16 positive monocytes and M-MDSC were restored after only three weeks of anti-TB treatment. Together, our findings show a link between the immunological status of TB patients and the levels of different circulating myeloid cell populations.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Alterations of myeloid cell populations have been reported in patients with tuberculosis (TB). In this work, we studied the relationship between myeloid-derived suppressor cells (MDSC) and monocytes subsets with the immunological responsiveness of TB patients. Individuals with active TB were classified as low responders (LR-TB) or high responders (HR-TB) according to their T cell responses against a cell lysate of (-Ag). Thus, LR-TB, individuals with severe disease, display a weaker immune response to compare to HR-TB, subjects with strong immunity against the bacteria. We observed that LR-TB presented higher percentages of CD16 positive monocytes as compared to HR-TB and healthy donors. Moreover, monocyte-like (M-MDSC) and polymorphonuclear-like (PMN-MDSC) MDSC were increased in patients and the proportion of M-MDSC inversely correlated with IFN-γ levels released after -Ag stimulation in HR-TB. We also found that LR-TB displayed the highest percentages of circulating M-MDSC. These results demonstrate that CD16 positive monocytes and M-MDSC frequencies could be used as another immunological classification parameter. Interestingly, in LR-TB, frequencies of CD16 positive monocytes and M-MDSC were restored after only three weeks of anti-TB treatment. Together, our findings show a link between the immunological status of TB patients and the levels of different circulating myeloid cell populations. |
2021
|
Pellegrini, Joaquín Miguel; Sabbione, Florencia; Morelli, María Paula; Tateosian, Nancy Liliana; Castello, Florencia Andrea; Amiano, Nicolás Oscar; Palmero, Domingo; Levi, Alberto; Ciallella, Lorena; Colombo, María Isabel; Trevani, Analía Silvina; García, Verónica Edith Neutrophil autophagy during human active tuberculosis is modulated by SLAMF1 Article de journal Dans: Autophagy, vol. 17, no. 9, p. 2629–2638, 2021, ISSN: 1554-8635. @article{pmid32954947,
title = {Neutrophil autophagy during human active tuberculosis is modulated by SLAMF1},
author = {Joaquín Miguel Pellegrini and Florencia Sabbione and María Paula Morelli and Nancy Liliana Tateosian and Florencia Andrea Castello and Nicolás Oscar Amiano and Domingo Palmero and Alberto Levi and Lorena Ciallella and María Isabel Colombo and Analía Silvina Trevani and Verónica Edith García},
doi = {10.1080/15548627.2020.1825273},
issn = {1554-8635},
year = {2021},
date = {2021-09-01},
urldate = {2021-09-01},
journal = {Autophagy},
volume = {17},
number = {9},
pages = {2629--2638},
abstract = {Neutrophils infected with () predominate in tuberculosis patients' lungs. Neutrophils phagocytose the pathogen, but the mechanism of pathogen elimination is controversial. Macroautophagy/autophagy, a crucial mechanism for several neutrophil functions, can be modulated by immunological mediators. The costimulatory molecule SLAMF1 can act as a microbial sensor in macrophages being also able to interact with autophagy-related proteins. Here, we demonstrate for the first time that human neutrophils express SLAMF1 upon -stimulation. Furthermore, SLAMF1 was found colocalizing with LC3B vesicles, and activation of SLAMF1 increased neutrophil autophagy induced by . Finally, tuberculosis patients' neutrophils displayed reduced levels of SLAMF1 and lower levels of autophagy against as compared to healthy controls. Altogether, these results indicate that SLAMF1 participates in neutrophil autophagy during active tuberculosis. AFB: acid-fast bacilli; BafA1: bafilomycin A; CLL: chronic lymphocytic leukemia; DPI: diphenyleneiodonium; EVs: extracellular vesicles; FBS: fetal bovine serum; HD: healthy donors; HR: high responder (tuberculosis patient); IFNG: interferon gamma; IL1B: interleukin 1 beta; IL17A: interleukin 17A; IL8: interleukin 8; LR: low responder (tuberculosis patient); mAb: monoclonal antibody; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; MAPK: mitogen-activated protein kinase; MAPK1/ERK2: mitogen-activated protein kinase 1; MAPK14/p38: mitogen-activated protein kinase 14; tuberculosis; Ag: , Strain H37Rv, whole cell lysate; NETs: neutrophils extracellular traps; PPD: purified protein derivative; ROS: reactive oxygen species; PIK3C3/VPS34: phosphatidylinositol 3-kinase catalytic subunit type 3; SLAMF1: signaling lymphocytic activation molecule family member 1; TB: tuberculosis; TLR: toll like receptor.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Neutrophils infected with () predominate in tuberculosis patients' lungs. Neutrophils phagocytose the pathogen, but the mechanism of pathogen elimination is controversial. Macroautophagy/autophagy, a crucial mechanism for several neutrophil functions, can be modulated by immunological mediators. The costimulatory molecule SLAMF1 can act as a microbial sensor in macrophages being also able to interact with autophagy-related proteins. Here, we demonstrate for the first time that human neutrophils express SLAMF1 upon -stimulation. Furthermore, SLAMF1 was found colocalizing with LC3B vesicles, and activation of SLAMF1 increased neutrophil autophagy induced by . Finally, tuberculosis patients' neutrophils displayed reduced levels of SLAMF1 and lower levels of autophagy against as compared to healthy controls. Altogether, these results indicate that SLAMF1 participates in neutrophil autophagy during active tuberculosis. AFB: acid-fast bacilli; BafA1: bafilomycin A; CLL: chronic lymphocytic leukemia; DPI: diphenyleneiodonium; EVs: extracellular vesicles; FBS: fetal bovine serum; HD: healthy donors; HR: high responder (tuberculosis patient); IFNG: interferon gamma; IL1B: interleukin 1 beta; IL17A: interleukin 17A; IL8: interleukin 8; LR: low responder (tuberculosis patient); mAb: monoclonal antibody; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; MAPK: mitogen-activated protein kinase; MAPK1/ERK2: mitogen-activated protein kinase 1; MAPK14/p38: mitogen-activated protein kinase 14; tuberculosis; Ag: , Strain H37Rv, whole cell lysate; NETs: neutrophils extracellular traps; PPD: purified protein derivative; ROS: reactive oxygen species; PIK3C3/VPS34: phosphatidylinositol 3-kinase catalytic subunit type 3; SLAMF1: signaling lymphocytic activation molecule family member 1; TB: tuberculosis; TLR: toll like receptor. |
Pellegrini, Joaquín Miguel; Martin, Candela; Morelli, María Paula; Schander, Julieta Aylen; Tateosian, Nancy Liliana; Amiano, Nicolás Oscar; Rolandelli, Agustín; Palmero, Domingo Juan; Levi, Alberto; Ciallella, Lorena; Colombo, María Isabel; García, Verónica Edith PGE2 displays immunosuppressive effects during human active tuberculosis Article de journal Dans: Sci Rep, vol. 11, no. 1, p. 13559, 2021, ISSN: 2045-2322. @article{pmid34193890,
title = {PGE2 displays immunosuppressive effects during human active tuberculosis},
author = {Joaquín Miguel Pellegrini and Candela Martin and María Paula Morelli and Julieta Aylen Schander and Nancy Liliana Tateosian and Nicolás Oscar Amiano and Agustín Rolandelli and Domingo Juan Palmero and Alberto Levi and Lorena Ciallella and María Isabel Colombo and Verónica Edith García},
doi = {10.1038/s41598-021-92667-1},
issn = {2045-2322},
year = {2021},
date = {2021-06-01},
urldate = {2021-06-01},
journal = {Sci Rep},
volume = {11},
number = {1},
pages = {13559},
abstract = {Prostaglandin E2 (PGE2), an active lipid compound derived from arachidonic acid, regulates different stages of the immune response of the host during several pathologies such as chronic infections or cancer. In fact, manipulation of PGE2 levels was proposed as an approach for countering the Type I IFN signature of tuberculosis (TB). However, very limited information regarding the PGE2 pathway in patients with active TB is currently available. In the present work, we demonstrated that PGE2 exerts a potent immunosuppressive action during the immune response of the human host against Mycobacterium tuberculosis (Mtb) infection. Actually, we showed that PGE2 significantly reduced the surface expression of several immunological receptors, the lymphoproliferation and the production of proinflammatory cytokines. In addition, PGE2 promoted autophagy in monocytes and neutrophils cultured with Mtb antigens. These results suggest that PGE2 might be attenuating the excessive inflammatory immune response caused by Mtb, emerging as an attractive therapeutic target. Taken together, our findings contribute to the knowledge of the role of PGE2 in the human host resistance to Mtb and highlight the potential of this lipid mediator as a tool to improve anti-TB treatment.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Prostaglandin E2 (PGE2), an active lipid compound derived from arachidonic acid, regulates different stages of the immune response of the host during several pathologies such as chronic infections or cancer. In fact, manipulation of PGE2 levels was proposed as an approach for countering the Type I IFN signature of tuberculosis (TB). However, very limited information regarding the PGE2 pathway in patients with active TB is currently available. In the present work, we demonstrated that PGE2 exerts a potent immunosuppressive action during the immune response of the human host against Mycobacterium tuberculosis (Mtb) infection. Actually, we showed that PGE2 significantly reduced the surface expression of several immunological receptors, the lymphoproliferation and the production of proinflammatory cytokines. In addition, PGE2 promoted autophagy in monocytes and neutrophils cultured with Mtb antigens. These results suggest that PGE2 might be attenuating the excessive inflammatory immune response caused by Mtb, emerging as an attractive therapeutic target. Taken together, our findings contribute to the knowledge of the role of PGE2 in the human host resistance to Mtb and highlight the potential of this lipid mediator as a tool to improve anti-TB treatment. |
Pellegrini, Joaquin Miguel; Tateosian, Nancy Liliana; Morelli, María Paula; García, Verónica Edith Shedding Light on Autophagy During Human Tuberculosis. A Long Way to Go Article de journal Dans: Front Cell Infect Microbiol, vol. 11, p. 820095, 2021, ISSN: 2235-2988. @article{pmid35071056,
title = {Shedding Light on Autophagy During Human Tuberculosis. A Long Way to Go},
author = {Joaquin Miguel Pellegrini and Nancy Liliana Tateosian and María Paula Morelli and Verónica Edith García},
doi = {10.3389/fcimb.2021.820095},
issn = {2235-2988},
year = {2021},
date = {2021-01-01},
urldate = {2021-01-01},
journal = {Front Cell Infect Microbiol},
volume = {11},
pages = {820095},
abstract = {Immunity against () is highly complex, and the outcome of the infection depends on the role of several immune mediators with particular temporal dynamics on the host microenvironment. Autophagy is a central homeostatic mechanism that plays a role on immunity against intracellular pathogens, including . Enhanced autophagy in macrophages mediates elimination of intracellular through lytic and antimicrobial properties only found in autolysosomes. Additionally, it has been demonstrated that standard anti-tuberculosis chemotherapy depends on host autophagy to coordinate successful antimicrobial responses to mycobacteria. Notably, autophagy constitutes an anti-inflammatory mechanism that protects against endomembrane damage triggered by several endogenous components or infectious agents and precludes excessive inflammation. It has also been reported that autophagy can be modulated by cytokines and other immunological signals. Most of the studies on autophagy as a defense mechanism against have been performed using murine models or human cell lines. However, very limited information exists about the autophagic response in cells from tuberculosis patients. Herein, we review studies that face the autophagy process in tuberculosis patients as a component of the immune response of the human host against an intracellular microorganism such as . Interestingly, these findings might contribute to recognize new targets for the development of novel therapeutic tools to combat . Actually, either as a potential successful vaccine or a complementary immunotherapy, efforts are needed to further elucidate the role of autophagy during the immune response of the human host, which will allow to achieve protective and therapeutic benefits in human tuberculosis.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Immunity against () is highly complex, and the outcome of the infection depends on the role of several immune mediators with particular temporal dynamics on the host microenvironment. Autophagy is a central homeostatic mechanism that plays a role on immunity against intracellular pathogens, including . Enhanced autophagy in macrophages mediates elimination of intracellular through lytic and antimicrobial properties only found in autolysosomes. Additionally, it has been demonstrated that standard anti-tuberculosis chemotherapy depends on host autophagy to coordinate successful antimicrobial responses to mycobacteria. Notably, autophagy constitutes an anti-inflammatory mechanism that protects against endomembrane damage triggered by several endogenous components or infectious agents and precludes excessive inflammation. It has also been reported that autophagy can be modulated by cytokines and other immunological signals. Most of the studies on autophagy as a defense mechanism against have been performed using murine models or human cell lines. However, very limited information exists about the autophagic response in cells from tuberculosis patients. Herein, we review studies that face the autophagy process in tuberculosis patients as a component of the immune response of the human host against an intracellular microorganism such as . Interestingly, these findings might contribute to recognize new targets for the development of novel therapeutic tools to combat . Actually, either as a potential successful vaccine or a complementary immunotherapy, efforts are needed to further elucidate the role of autophagy during the immune response of the human host, which will allow to achieve protective and therapeutic benefits in human tuberculosis. |
2017
|
Tateosian, Nancy Liliana; Pellegrini, Joaquín Miguel; Amiano, Nicolás Oscar; Rolandelli, Agustín; Casco, Nicolás; Palmero, Domingo Juan; Colombo, María Isabel; García, Verónica Edith IL17A augments autophagy in Mycobacterium tuberculosis-infected monocytes from patients with active tuberculosis in association with the severity of the disease Article de journal Dans: Autophagy, vol. 13, no. 7, p. 1191–1204, 2017, ISSN: 1554-8635. @article{pmid28581888,
title = {IL17A augments autophagy in Mycobacterium tuberculosis-infected monocytes from patients with active tuberculosis in association with the severity of the disease},
author = {Nancy Liliana Tateosian and Joaquín Miguel Pellegrini and Nicolás Oscar Amiano and Agustín Rolandelli and Nicolás Casco and Domingo Juan Palmero and María Isabel Colombo and Verónica Edith García},
doi = {10.1080/15548627.2017.1320636},
issn = {1554-8635},
year = {2017},
date = {2017-07-01},
urldate = {2017-07-01},
journal = {Autophagy},
volume = {13},
number = {7},
pages = {1191--1204},
abstract = {During mycobacterial infection, macroautophagy/autophagy, a process modulated by cytokines, is essential for mounting successful host responses. Autophagy collaborates with human immune responses against Mycobacterium tuberculosis (Mt) in association with specific IFNG secreted against the pathogen. However, IFNG alone is not sufficient to the complete bacterial eradication, and other cytokines might be required. Actually, induction of Th1 and Th17 immune responses are required for protection against Mt. Accordingly, we showed that IL17A and IFNG expression in lymphocytes from tuberculosis patients correlates with disease severity. Here we investigate the role of IFNG and IL17A during autophagy in monocytes infected with Mt H37Rv or the mutant MtΔRD1. Patients with active disease were classified as high responder (HR) or low responder (LR) according to their T cell responses against Mt. IL17A augmented autophagy in infected monocytes from HR patients through a mechanism that activated MAPK1/ERK2-MAPK3/ERK1 but, during infection of monocytes from LR patients, IL17A had no effect on the autophagic response. In contrast, addition of IFNG to infected monocytes, increased autophagy by activating MAPK14/p38 α both in HR and LR patients. Interestingly, proteins codified in the RD1 region did not interfere with IFNG and IL17A autophagy induction. Therefore, in severe tuberculosis patients' monocytes, IL17A was unable to augment autophagy because of a defect in the MAPK1/3 signaling pathway. In contrast, both IFNG and IL17A increased autophagy levels in patients with strong immunity to Mt, promoting mycobacterial killing. Our findings might contribute to recognize new targets for the development of novel therapeutic tools to fight the pathogen.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
During mycobacterial infection, macroautophagy/autophagy, a process modulated by cytokines, is essential for mounting successful host responses. Autophagy collaborates with human immune responses against Mycobacterium tuberculosis (Mt) in association with specific IFNG secreted against the pathogen. However, IFNG alone is not sufficient to the complete bacterial eradication, and other cytokines might be required. Actually, induction of Th1 and Th17 immune responses are required for protection against Mt. Accordingly, we showed that IL17A and IFNG expression in lymphocytes from tuberculosis patients correlates with disease severity. Here we investigate the role of IFNG and IL17A during autophagy in monocytes infected with Mt H37Rv or the mutant MtΔRD1. Patients with active disease were classified as high responder (HR) or low responder (LR) according to their T cell responses against Mt. IL17A augmented autophagy in infected monocytes from HR patients through a mechanism that activated MAPK1/ERK2-MAPK3/ERK1 but, during infection of monocytes from LR patients, IL17A had no effect on the autophagic response. In contrast, addition of IFNG to infected monocytes, increased autophagy by activating MAPK14/p38 α both in HR and LR patients. Interestingly, proteins codified in the RD1 region did not interfere with IFNG and IL17A autophagy induction. Therefore, in severe tuberculosis patients' monocytes, IL17A was unable to augment autophagy because of a defect in the MAPK1/3 signaling pathway. In contrast, both IFNG and IL17A increased autophagy levels in patients with strong immunity to Mt, promoting mycobacterial killing. Our findings might contribute to recognize new targets for the development of novel therapeutic tools to fight the pathogen. |
