Galectin-1-driven tolerogenic programs aggravate yersinia enterocolitica infection by repressing antibacterial immunity
Yersinia enterocolitica is an enteropathogenic bacterium that causes gastrointestinal disorders, as well as extraintestinal manifestations. To subvert the host's immune response, Y. enterocolitica uses a type III secretion system consisting of an injectisome and effector proteins, called Yersin...
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todo:paper_00221767_v199_n4_p1382_Davicino2023-10-03T14:28:01Z Galectin-1-driven tolerogenic programs aggravate yersinia enterocolitica infection by repressing antibacterial immunity Davicino, R.C. Méndez-Huergo, S.P. Eliçabe, R.J. Stupirski, J.C. Autenrieth, I. Di Genaro, M.S. Rabinovich, G.A. bacterial protein galectin 1 gamma interferon immunoglobulin enhancer binding protein interleukin 17 nitric oxide outer membrane protein protein tyrosine phosphatase tumor necrosis factor yopH protein, Yersinia YopP protein, Yersinia animal antagonists and inhibitors bacterial load biosynthesis blood deficiency genetics host pathogen interaction immunology intestine metabolism microbiology mouse pathology Peyer patch spleen Yersinia enterocolitica Yersinia infection Animals Bacterial Load Bacterial Outer Membrane Proteins Bacterial Proteins Galectin 1 Host-Pathogen Interactions Interferon-gamma Interleukin-17 Intestines Mice NF-kappa B Nitric Oxide Peyer's Patches Protein Tyrosine Phosphatases Spleen Tumor Necrosis Factor-alpha Yersinia enterocolitica Yersinia Infections Yersinia enterocolitica is an enteropathogenic bacterium that causes gastrointestinal disorders, as well as extraintestinal manifestations. To subvert the host's immune response, Y. enterocolitica uses a type III secretion system consisting of an injectisome and effector proteins, called Yersinia outer proteins (Yops), that modulate activation, signaling, and survival of immune cells. In this article, we show that galectin-1 (Gal-1), an immunoregulatory lectin widely expressed in mucosal tissues, contributes to Y. enterocolitica pathogenicity by undermining protective antibacterial responses. We found higher expression of Gal-1 in the spleen and Peyer's patches of mice infected orogastrically with Y. enterocolitica serotype O:8 compared with noninfected hosts. This effect was prevented when mice were infected with Y. enterocolitica lacking YopP or YopH, two critical effectors involved in bacterial immune evasion. Consistent with a regulatory role for this lectin during Y. enterocolitica pathogenesis, mice lacking Gal-1 showed increased weight and survival, lower bacterial load, and attenuated intestinal pathology compared with wild-type mice. These protective effects involved modulation of NF-kB activation, TNF production, and NO synthesis in mucosal tissue and macrophages, as well as systemic dysregulation of IL-17 and IFN-γ responses. In vivo neutralization of these proinflammatory cytokines impaired bacterial clearance and eliminated host protection conferred by Gal-1 deficiency. Finally, supplementation of recombinant Gal-1 in mice lacking Gal-1 or treatment of wild-type mice with a neutralizing anti-Gal-1 mAb confirmed the immune inhibitory role of this endogenous lectin during Y. enterocolitica infection. Thus, targeting Gal-1-glycan interactions may contribute to reinforce antibacterial responses by reprogramming innate and adaptive immune mechanisms. Copyright © 2017 by The American Association of Immunologists, Inc. JOUR info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/2.5/ar http://hdl.handle.net/20.500.12110/paper_00221767_v199_n4_p1382_Davicino |
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Universidad de Buenos Aires |
| institution_str |
I-28 |
| repository_str |
R-134 |
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Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
| topic |
bacterial protein galectin 1 gamma interferon immunoglobulin enhancer binding protein interleukin 17 nitric oxide outer membrane protein protein tyrosine phosphatase tumor necrosis factor yopH protein, Yersinia YopP protein, Yersinia animal antagonists and inhibitors bacterial load biosynthesis blood deficiency genetics host pathogen interaction immunology intestine metabolism microbiology mouse pathology Peyer patch spleen Yersinia enterocolitica Yersinia infection Animals Bacterial Load Bacterial Outer Membrane Proteins Bacterial Proteins Galectin 1 Host-Pathogen Interactions Interferon-gamma Interleukin-17 Intestines Mice NF-kappa B Nitric Oxide Peyer's Patches Protein Tyrosine Phosphatases Spleen Tumor Necrosis Factor-alpha Yersinia enterocolitica Yersinia Infections |
| spellingShingle |
bacterial protein galectin 1 gamma interferon immunoglobulin enhancer binding protein interleukin 17 nitric oxide outer membrane protein protein tyrosine phosphatase tumor necrosis factor yopH protein, Yersinia YopP protein, Yersinia animal antagonists and inhibitors bacterial load biosynthesis blood deficiency genetics host pathogen interaction immunology intestine metabolism microbiology mouse pathology Peyer patch spleen Yersinia enterocolitica Yersinia infection Animals Bacterial Load Bacterial Outer Membrane Proteins Bacterial Proteins Galectin 1 Host-Pathogen Interactions Interferon-gamma Interleukin-17 Intestines Mice NF-kappa B Nitric Oxide Peyer's Patches Protein Tyrosine Phosphatases Spleen Tumor Necrosis Factor-alpha Yersinia enterocolitica Yersinia Infections Davicino, R.C. Méndez-Huergo, S.P. Eliçabe, R.J. Stupirski, J.C. Autenrieth, I. Di Genaro, M.S. Rabinovich, G.A. Galectin-1-driven tolerogenic programs aggravate yersinia enterocolitica infection by repressing antibacterial immunity |
| topic_facet |
bacterial protein galectin 1 gamma interferon immunoglobulin enhancer binding protein interleukin 17 nitric oxide outer membrane protein protein tyrosine phosphatase tumor necrosis factor yopH protein, Yersinia YopP protein, Yersinia animal antagonists and inhibitors bacterial load biosynthesis blood deficiency genetics host pathogen interaction immunology intestine metabolism microbiology mouse pathology Peyer patch spleen Yersinia enterocolitica Yersinia infection Animals Bacterial Load Bacterial Outer Membrane Proteins Bacterial Proteins Galectin 1 Host-Pathogen Interactions Interferon-gamma Interleukin-17 Intestines Mice NF-kappa B Nitric Oxide Peyer's Patches Protein Tyrosine Phosphatases Spleen Tumor Necrosis Factor-alpha Yersinia enterocolitica Yersinia Infections |
| description |
Yersinia enterocolitica is an enteropathogenic bacterium that causes gastrointestinal disorders, as well as extraintestinal manifestations. To subvert the host's immune response, Y. enterocolitica uses a type III secretion system consisting of an injectisome and effector proteins, called Yersinia outer proteins (Yops), that modulate activation, signaling, and survival of immune cells. In this article, we show that galectin-1 (Gal-1), an immunoregulatory lectin widely expressed in mucosal tissues, contributes to Y. enterocolitica pathogenicity by undermining protective antibacterial responses. We found higher expression of Gal-1 in the spleen and Peyer's patches of mice infected orogastrically with Y. enterocolitica serotype O:8 compared with noninfected hosts. This effect was prevented when mice were infected with Y. enterocolitica lacking YopP or YopH, two critical effectors involved in bacterial immune evasion. Consistent with a regulatory role for this lectin during Y. enterocolitica pathogenesis, mice lacking Gal-1 showed increased weight and survival, lower bacterial load, and attenuated intestinal pathology compared with wild-type mice. These protective effects involved modulation of NF-kB activation, TNF production, and NO synthesis in mucosal tissue and macrophages, as well as systemic dysregulation of IL-17 and IFN-γ responses. In vivo neutralization of these proinflammatory cytokines impaired bacterial clearance and eliminated host protection conferred by Gal-1 deficiency. Finally, supplementation of recombinant Gal-1 in mice lacking Gal-1 or treatment of wild-type mice with a neutralizing anti-Gal-1 mAb confirmed the immune inhibitory role of this endogenous lectin during Y. enterocolitica infection. Thus, targeting Gal-1-glycan interactions may contribute to reinforce antibacterial responses by reprogramming innate and adaptive immune mechanisms. Copyright © 2017 by The American Association of Immunologists, Inc. |
| format |
JOUR |
| author |
Davicino, R.C. Méndez-Huergo, S.P. Eliçabe, R.J. Stupirski, J.C. Autenrieth, I. Di Genaro, M.S. Rabinovich, G.A. |
| author_facet |
Davicino, R.C. Méndez-Huergo, S.P. Eliçabe, R.J. Stupirski, J.C. Autenrieth, I. Di Genaro, M.S. Rabinovich, G.A. |
| author_sort |
Davicino, R.C. |
| title |
Galectin-1-driven tolerogenic programs aggravate yersinia enterocolitica infection by repressing antibacterial immunity |
| title_short |
Galectin-1-driven tolerogenic programs aggravate yersinia enterocolitica infection by repressing antibacterial immunity |
| title_full |
Galectin-1-driven tolerogenic programs aggravate yersinia enterocolitica infection by repressing antibacterial immunity |
| title_fullStr |
Galectin-1-driven tolerogenic programs aggravate yersinia enterocolitica infection by repressing antibacterial immunity |
| title_full_unstemmed |
Galectin-1-driven tolerogenic programs aggravate yersinia enterocolitica infection by repressing antibacterial immunity |
| title_sort |
galectin-1-driven tolerogenic programs aggravate yersinia enterocolitica infection by repressing antibacterial immunity |
| url |
http://hdl.handle.net/20.500.12110/paper_00221767_v199_n4_p1382_Davicino |
| work_keys_str_mv |
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| _version_ |
1807324286512267264 |