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Galectin-1 Impairs the Generation of Anti-Parasitic Th1 Cell Responses in the Liver during Experimental Visceral Leishmaniasis
Many infectious diseases are characterized by the development of immunoregulatory pathways that contribute to pathogen persistence and associated disease symptoms. In diseases caused by intracellular parasites, such as visceral leishmaniasis (VL), various immune modulators have the capacity to negat...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5643427/ https://www.ncbi.nlm.nih.gov/pubmed/29075269 http://dx.doi.org/10.3389/fimmu.2017.01307 |
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author | Bunn, Patrick T. Montes de Oca, Marcela Rivera, Fabian de Labastida Kumar, Rajiv Edwards, Chelsea L. Faleiro, Rebecca J. Ng, Susanna S. Sheel, Meru Wang, Yulin Amante, Fiona H. Haque, Ashraful Engwerda, Christian R. |
author_facet | Bunn, Patrick T. Montes de Oca, Marcela Rivera, Fabian de Labastida Kumar, Rajiv Edwards, Chelsea L. Faleiro, Rebecca J. Ng, Susanna S. Sheel, Meru Wang, Yulin Amante, Fiona H. Haque, Ashraful Engwerda, Christian R. |
author_sort | Bunn, Patrick T. |
collection | PubMed |
description | Many infectious diseases are characterized by the development of immunoregulatory pathways that contribute to pathogen persistence and associated disease symptoms. In diseases caused by intracellular parasites, such as visceral leishmaniasis (VL), various immune modulators have the capacity to negatively impact protective CD4(+) T cell functions. Galectin-1 is widely expressed on immune cells and has previously been shown to suppress inflammatory responses and promote the development of CD4(+) T cells with immunoregulatory characteristics. Here, we investigated the role of galectin-1 in experimental VL caused by infection of C57BL/6 mice with Leishmania donovani. Mice lacking galectin-1 expression exhibited enhanced tissue-specific control of parasite growth in the liver, associated with an augmented Th1 cell response. However, unlike reports in other experimental models, we found little role for galectin-1 in the generation of IL-10-producing Th1 (Tr1) cells, and instead report that galectin-1 suppressed hepatic Th1 cell development. Furthermore, we found relatively early effects of galectin-1 deficiency on parasite growth, suggesting involvement of innate immune cells. However, experiments investigating the impact of galectin-1 deficiency on dendritic cells indicated that they were not responsible for the phenotypes observed in galectin-1-deficient mice. Instead, studies examining galectin-1 expression by CD4(+) T cells supported a T cell intrinsic role for galectin-1 in the suppression of hepatic Th1 cell development during experimental VL. Together, our findings provide new information on the roles of galectin-1 during parasitic infection and indicate an important role for this molecule in tissue-specific Th1 cell development, but not CD4(+) T cell IL-10 production. |
format | Online Article Text |
id | pubmed-5643427 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-56434272017-10-26 Galectin-1 Impairs the Generation of Anti-Parasitic Th1 Cell Responses in the Liver during Experimental Visceral Leishmaniasis Bunn, Patrick T. Montes de Oca, Marcela Rivera, Fabian de Labastida Kumar, Rajiv Edwards, Chelsea L. Faleiro, Rebecca J. Ng, Susanna S. Sheel, Meru Wang, Yulin Amante, Fiona H. Haque, Ashraful Engwerda, Christian R. Front Immunol Immunology Many infectious diseases are characterized by the development of immunoregulatory pathways that contribute to pathogen persistence and associated disease symptoms. In diseases caused by intracellular parasites, such as visceral leishmaniasis (VL), various immune modulators have the capacity to negatively impact protective CD4(+) T cell functions. Galectin-1 is widely expressed on immune cells and has previously been shown to suppress inflammatory responses and promote the development of CD4(+) T cells with immunoregulatory characteristics. Here, we investigated the role of galectin-1 in experimental VL caused by infection of C57BL/6 mice with Leishmania donovani. Mice lacking galectin-1 expression exhibited enhanced tissue-specific control of parasite growth in the liver, associated with an augmented Th1 cell response. However, unlike reports in other experimental models, we found little role for galectin-1 in the generation of IL-10-producing Th1 (Tr1) cells, and instead report that galectin-1 suppressed hepatic Th1 cell development. Furthermore, we found relatively early effects of galectin-1 deficiency on parasite growth, suggesting involvement of innate immune cells. However, experiments investigating the impact of galectin-1 deficiency on dendritic cells indicated that they were not responsible for the phenotypes observed in galectin-1-deficient mice. Instead, studies examining galectin-1 expression by CD4(+) T cells supported a T cell intrinsic role for galectin-1 in the suppression of hepatic Th1 cell development during experimental VL. Together, our findings provide new information on the roles of galectin-1 during parasitic infection and indicate an important role for this molecule in tissue-specific Th1 cell development, but not CD4(+) T cell IL-10 production. Frontiers Media S.A. 2017-10-12 /pmc/articles/PMC5643427/ /pubmed/29075269 http://dx.doi.org/10.3389/fimmu.2017.01307 Text en Copyright © 2017 Bunn, Montes de Oca, Rivera, Kumar, Edwards, Faleiro, Ng, Sheel, Wang, Amante, Haque and Engwerda. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Immunology Bunn, Patrick T. Montes de Oca, Marcela Rivera, Fabian de Labastida Kumar, Rajiv Edwards, Chelsea L. Faleiro, Rebecca J. Ng, Susanna S. Sheel, Meru Wang, Yulin Amante, Fiona H. Haque, Ashraful Engwerda, Christian R. Galectin-1 Impairs the Generation of Anti-Parasitic Th1 Cell Responses in the Liver during Experimental Visceral Leishmaniasis |
title | Galectin-1 Impairs the Generation of Anti-Parasitic Th1 Cell Responses in the Liver during Experimental Visceral Leishmaniasis |
title_full | Galectin-1 Impairs the Generation of Anti-Parasitic Th1 Cell Responses in the Liver during Experimental Visceral Leishmaniasis |
title_fullStr | Galectin-1 Impairs the Generation of Anti-Parasitic Th1 Cell Responses in the Liver during Experimental Visceral Leishmaniasis |
title_full_unstemmed | Galectin-1 Impairs the Generation of Anti-Parasitic Th1 Cell Responses in the Liver during Experimental Visceral Leishmaniasis |
title_short | Galectin-1 Impairs the Generation of Anti-Parasitic Th1 Cell Responses in the Liver during Experimental Visceral Leishmaniasis |
title_sort | galectin-1 impairs the generation of anti-parasitic th1 cell responses in the liver during experimental visceral leishmaniasis |
topic | Immunology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5643427/ https://www.ncbi.nlm.nih.gov/pubmed/29075269 http://dx.doi.org/10.3389/fimmu.2017.01307 |
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