Trypanosoma cruzi infection imparts a regulatory program in dendritic cells and T cells via galectin-1-dependent mechanisms
Galectin-1 (Gal-1), an endogenous glycan-binding protein, is widely distributed at sites of inflammation and microbial invasion. Despite considerable progress regarding the immunoregulatory activity of this lectin, the role of endogenous Gal-1 during acute parasite infections is uncertain. In this s...
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paper:paper_00221767_v195_n7_p3311_Poncini2023-06-08T14:46:58Z Trypanosoma cruzi infection imparts a regulatory program in dendritic cells and T cells via galectin-1-dependent mechanisms Ilarregui, Juan Martín Cucher, Marcela Alejandra CD4 antigen galectin 1 interleukin 10 interleukin 17 interleukin 2 receptor alpha transcription factor FOXP3 transforming growth factor beta1 galectin 1 gamma interferon IDO1 protein, mouse IL10 protein, mouse indoleamine 2,3 dioxygenase interleukin 10 Pdcd1lg2 protein, mouse programmed death 1 ligand 2 transforming growth factor beta1 analysis of variance animal cell animal experiment animal model animal tissue Article CD8+ T lymphocyte cell activation cell differentiation cell survival cell viability Chagas disease confocal microscopy controlled study cytokine production dendritic cell disease predisposition glycosylation homeostasis immunoblotting immunogenicity immunomodulation lymphocyte proliferation male mononuclear cell mouse nonhuman pathogen load priority journal protein analysis protein binding protein function quantitative analysis real time polymerase chain reaction T lymphocyte Th1 cell Th17 cell upregulation animal Bagg albino mouse biosynthesis C3H mouse Chagas disease cytology dendritic cell genetics immunology knockout mouse lymph node metabolism mortality parasite load parasitology regulatory T lymphocyte Trypanosoma cruzi Animals CD8-Positive T-Lymphocytes Chagas Disease Dendritic Cells Galectin 1 Indoleamine-Pyrrole 2,3,-Dioxygenase Interferon-gamma Interleukin-10 Lymph Nodes Male Mice Mice, Inbred BALB C Mice, Inbred C3H Mice, Knockout Parasite Load Programmed Cell Death 1 Ligand 2 Protein T-Lymphocytes, Regulatory Transforming Growth Factor beta1 Trypanosoma cruzi Galectin-1 (Gal-1), an endogenous glycan-binding protein, is widely distributed at sites of inflammation and microbial invasion. Despite considerable progress regarding the immunoregulatory activity of this lectin, the role of endogenous Gal-1 during acute parasite infections is uncertain. In this study, we show that Gal-1 functions as a negative regulator to limit host-protective immunity following intradermal infection with Trypanosoma cruzi. Concomitant with the upregulation of immune inhibitory mediators, including IL-10, TGF-β1, IDO, and programmed death ligand 2, T. cruzi infection induced an early increase of Gal-1 expression in vivo. Compared to their wild-type (WT) counterpart, Gal-1-deficient (Lgals1-/-) mice exhibited reduced mortality and lower parasite load in muscle tissue. Resistance of Lgals1-/- mice to T. cruzi infection was associated with a failure in the activation of Gal-1-driven tolerogenic circuits, otherwise orchestrated by WT dendritic cells, leading to secondary dysfunction in the induction of CD4+CD25+Foxp3+ regulatory T cells. This effect was accompanied by an increased number of CD8+ T cells and higher frequency of IFN-γ-producing CD4+ T cells in muscle tissues and draining lymph nodes as well as reduced parasite burden in heart and hindlimb skeletal muscle. Moreover, dendritic cells lacking Gal-1 interrupted the Gal-1-mediated tolerogenic circuit and reinforced T cell-dependent anti-parasite immunity when adoptively transferred into WT mice. Thus, endogenous Gal-1 may influence T. cruzi infection by fueling tolerogenic circuits that hinder anti-parasite immunity. Fil:Ilarregui, J.M. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Cucher, M.A. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. 2015 https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00221767_v195_n7_p3311_Poncini http://hdl.handle.net/20.500.12110/paper_00221767_v195_n7_p3311_Poncini |
| institution |
Universidad de Buenos Aires |
| institution_str |
I-28 |
| repository_str |
R-134 |
| collection |
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
| topic |
CD4 antigen galectin 1 interleukin 10 interleukin 17 interleukin 2 receptor alpha transcription factor FOXP3 transforming growth factor beta1 galectin 1 gamma interferon IDO1 protein, mouse IL10 protein, mouse indoleamine 2,3 dioxygenase interleukin 10 Pdcd1lg2 protein, mouse programmed death 1 ligand 2 transforming growth factor beta1 analysis of variance animal cell animal experiment animal model animal tissue Article CD8+ T lymphocyte cell activation cell differentiation cell survival cell viability Chagas disease confocal microscopy controlled study cytokine production dendritic cell disease predisposition glycosylation homeostasis immunoblotting immunogenicity immunomodulation lymphocyte proliferation male mononuclear cell mouse nonhuman pathogen load priority journal protein analysis protein binding protein function quantitative analysis real time polymerase chain reaction T lymphocyte Th1 cell Th17 cell upregulation animal Bagg albino mouse biosynthesis C3H mouse Chagas disease cytology dendritic cell genetics immunology knockout mouse lymph node metabolism mortality parasite load parasitology regulatory T lymphocyte Trypanosoma cruzi Animals CD8-Positive T-Lymphocytes Chagas Disease Dendritic Cells Galectin 1 Indoleamine-Pyrrole 2,3,-Dioxygenase Interferon-gamma Interleukin-10 Lymph Nodes Male Mice Mice, Inbred BALB C Mice, Inbred C3H Mice, Knockout Parasite Load Programmed Cell Death 1 Ligand 2 Protein T-Lymphocytes, Regulatory Transforming Growth Factor beta1 Trypanosoma cruzi |
| spellingShingle |
CD4 antigen galectin 1 interleukin 10 interleukin 17 interleukin 2 receptor alpha transcription factor FOXP3 transforming growth factor beta1 galectin 1 gamma interferon IDO1 protein, mouse IL10 protein, mouse indoleamine 2,3 dioxygenase interleukin 10 Pdcd1lg2 protein, mouse programmed death 1 ligand 2 transforming growth factor beta1 analysis of variance animal cell animal experiment animal model animal tissue Article CD8+ T lymphocyte cell activation cell differentiation cell survival cell viability Chagas disease confocal microscopy controlled study cytokine production dendritic cell disease predisposition glycosylation homeostasis immunoblotting immunogenicity immunomodulation lymphocyte proliferation male mononuclear cell mouse nonhuman pathogen load priority journal protein analysis protein binding protein function quantitative analysis real time polymerase chain reaction T lymphocyte Th1 cell Th17 cell upregulation animal Bagg albino mouse biosynthesis C3H mouse Chagas disease cytology dendritic cell genetics immunology knockout mouse lymph node metabolism mortality parasite load parasitology regulatory T lymphocyte Trypanosoma cruzi Animals CD8-Positive T-Lymphocytes Chagas Disease Dendritic Cells Galectin 1 Indoleamine-Pyrrole 2,3,-Dioxygenase Interferon-gamma Interleukin-10 Lymph Nodes Male Mice Mice, Inbred BALB C Mice, Inbred C3H Mice, Knockout Parasite Load Programmed Cell Death 1 Ligand 2 Protein T-Lymphocytes, Regulatory Transforming Growth Factor beta1 Trypanosoma cruzi Ilarregui, Juan Martín Cucher, Marcela Alejandra Trypanosoma cruzi infection imparts a regulatory program in dendritic cells and T cells via galectin-1-dependent mechanisms |
| topic_facet |
CD4 antigen galectin 1 interleukin 10 interleukin 17 interleukin 2 receptor alpha transcription factor FOXP3 transforming growth factor beta1 galectin 1 gamma interferon IDO1 protein, mouse IL10 protein, mouse indoleamine 2,3 dioxygenase interleukin 10 Pdcd1lg2 protein, mouse programmed death 1 ligand 2 transforming growth factor beta1 analysis of variance animal cell animal experiment animal model animal tissue Article CD8+ T lymphocyte cell activation cell differentiation cell survival cell viability Chagas disease confocal microscopy controlled study cytokine production dendritic cell disease predisposition glycosylation homeostasis immunoblotting immunogenicity immunomodulation lymphocyte proliferation male mononuclear cell mouse nonhuman pathogen load priority journal protein analysis protein binding protein function quantitative analysis real time polymerase chain reaction T lymphocyte Th1 cell Th17 cell upregulation animal Bagg albino mouse biosynthesis C3H mouse Chagas disease cytology dendritic cell genetics immunology knockout mouse lymph node metabolism mortality parasite load parasitology regulatory T lymphocyte Trypanosoma cruzi Animals CD8-Positive T-Lymphocytes Chagas Disease Dendritic Cells Galectin 1 Indoleamine-Pyrrole 2,3,-Dioxygenase Interferon-gamma Interleukin-10 Lymph Nodes Male Mice Mice, Inbred BALB C Mice, Inbred C3H Mice, Knockout Parasite Load Programmed Cell Death 1 Ligand 2 Protein T-Lymphocytes, Regulatory Transforming Growth Factor beta1 Trypanosoma cruzi |
| description |
Galectin-1 (Gal-1), an endogenous glycan-binding protein, is widely distributed at sites of inflammation and microbial invasion. Despite considerable progress regarding the immunoregulatory activity of this lectin, the role of endogenous Gal-1 during acute parasite infections is uncertain. In this study, we show that Gal-1 functions as a negative regulator to limit host-protective immunity following intradermal infection with Trypanosoma cruzi. Concomitant with the upregulation of immune inhibitory mediators, including IL-10, TGF-β1, IDO, and programmed death ligand 2, T. cruzi infection induced an early increase of Gal-1 expression in vivo. Compared to their wild-type (WT) counterpart, Gal-1-deficient (Lgals1-/-) mice exhibited reduced mortality and lower parasite load in muscle tissue. Resistance of Lgals1-/- mice to T. cruzi infection was associated with a failure in the activation of Gal-1-driven tolerogenic circuits, otherwise orchestrated by WT dendritic cells, leading to secondary dysfunction in the induction of CD4+CD25+Foxp3+ regulatory T cells. This effect was accompanied by an increased number of CD8+ T cells and higher frequency of IFN-γ-producing CD4+ T cells in muscle tissues and draining lymph nodes as well as reduced parasite burden in heart and hindlimb skeletal muscle. Moreover, dendritic cells lacking Gal-1 interrupted the Gal-1-mediated tolerogenic circuit and reinforced T cell-dependent anti-parasite immunity when adoptively transferred into WT mice. Thus, endogenous Gal-1 may influence T. cruzi infection by fueling tolerogenic circuits that hinder anti-parasite immunity. |
| author |
Ilarregui, Juan Martín Cucher, Marcela Alejandra |
| author_facet |
Ilarregui, Juan Martín Cucher, Marcela Alejandra |
| author_sort |
Ilarregui, Juan Martín |
| title |
Trypanosoma cruzi infection imparts a regulatory program in dendritic cells and T cells via galectin-1-dependent mechanisms |
| title_short |
Trypanosoma cruzi infection imparts a regulatory program in dendritic cells and T cells via galectin-1-dependent mechanisms |
| title_full |
Trypanosoma cruzi infection imparts a regulatory program in dendritic cells and T cells via galectin-1-dependent mechanisms |
| title_fullStr |
Trypanosoma cruzi infection imparts a regulatory program in dendritic cells and T cells via galectin-1-dependent mechanisms |
| title_full_unstemmed |
Trypanosoma cruzi infection imparts a regulatory program in dendritic cells and T cells via galectin-1-dependent mechanisms |
| title_sort |
trypanosoma cruzi infection imparts a regulatory program in dendritic cells and t cells via galectin-1-dependent mechanisms |
| publishDate |
2015 |
| url |
https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00221767_v195_n7_p3311_Poncini http://hdl.handle.net/20.500.12110/paper_00221767_v195_n7_p3311_Poncini |
| work_keys_str_mv |
AT ilarreguijuanmartin trypanosomacruziinfectionimpartsaregulatoryprogramindendriticcellsandtcellsviagalectin1dependentmechanisms AT cuchermarcelaalejandra trypanosomacruziinfectionimpartsaregulatoryprogramindendriticcellsandtcellsviagalectin1dependentmechanisms |
| _version_ |
1768545588746387456 |