Immune exhaustion in chronic Chagas disease: Pro-inflammatory and immunomodulatory action of IL-27 in vitro.

In chronic Chagas disease, Trypanosoma cruzi-specific T-cell function decreases over time, and alterations in the homeostatic IL-7/IL-7R axis are evident, consistent with a process of immune exhaustion. IL-27 is an important immunoregulatory cytokine that shares T-cell signaling with IL-7 and other...

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Autores principales:	María Ailén Natale, Todd Minning, María Cecilia Albareda, Melisa Daiana Castro Eiro, María Gabriela Álvarez, Bruno Lococo, Gonzalo Cesar, Graciela Bertocchi, María Josefina Elias, María Belén Caputo, Rick Lee Tarleton, Susana Adriana Laucella
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270
Acceso en línea:	https://doaj.org/article/06691cc146b74fb197bcc2de737d9ef4
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spelling	oai:doaj.org-article:06691cc146b74fb197bcc2de737d9ef42021-11-25T06:33:10ZImmune exhaustion in chronic Chagas disease: Pro-inflammatory and immunomodulatory action of IL-27 in vitro.1935-27271935-273510.1371/journal.pntd.0009473https://doaj.org/article/06691cc146b74fb197bcc2de737d9ef42021-06-01T00:00:00Zhttps://doi.org/10.1371/journal.pntd.0009473https://doaj.org/toc/1935-2727https://doaj.org/toc/1935-2735In chronic Chagas disease, Trypanosoma cruzi-specific T-cell function decreases over time, and alterations in the homeostatic IL-7/IL-7R axis are evident, consistent with a process of immune exhaustion. IL-27 is an important immunoregulatory cytokine that shares T-cell signaling with IL-7 and other cytokines of the IL-12 family and might be involved in the transcriptional regulation of T-cell function. Here, we evaluated the expression and function of IL-27R in antigen-experienced T cells from subjects with chronic Chagas disease and assessed whether in vitro treatment with IL-27 and IL-7 might improve T. cruzi-specific polyfunctional T-cell responses. In vitro exposure of PBMCs to T. cruzi induced a downregulation of IL-27R in CD4+ T cells and an upregulation in CD8+ T cells in subjects without heart disease, while IL-27R expression remained unaltered in subjects with more severe clinical stages. The modulation of IL-27R was associated with functional signaling through STAT3 and STAT5 and induction of the downstream genes TBX21, EOMES and CXCL9 in response to IL-27. In vitro treatment of PBMCs with IL-27 and IL-7 improved monofunctional and polyfunctional Th1 responses, accompanied by the induction of IL-10 and Bcl-2 expression in subjects without heart disease but did not improve those in subjects with cardiomyopathy. Our findings support the process of desensitization of the IL-27/IL-27R pathway along with disease severity and that the pro-inflammatory and immunomodulatory mechanisms of IL-27 might be interconnected.María Ailén NataleTodd MinningMaría Cecilia AlbaredaMelisa Daiana Castro EiroMaría Gabriela ÁlvarezBruno LococoGonzalo CesarGraciela BertocchiMaría Josefina EliasMaría Belén CaputoRick Lee TarletonSusana Adriana LaucellaPublic Library of Science (PLoS)articleArctic medicine. Tropical medicineRC955-962Public aspects of medicineRA1-1270ENPLoS Neglected Tropical Diseases, Vol 15, Iss 6, p e0009473 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270
spellingShingle	Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 María Ailén Natale Todd Minning María Cecilia Albareda Melisa Daiana Castro Eiro María Gabriela Álvarez Bruno Lococo Gonzalo Cesar Graciela Bertocchi María Josefina Elias María Belén Caputo Rick Lee Tarleton Susana Adriana Laucella Immune exhaustion in chronic Chagas disease: Pro-inflammatory and immunomodulatory action of IL-27 in vitro.
description	In chronic Chagas disease, Trypanosoma cruzi-specific T-cell function decreases over time, and alterations in the homeostatic IL-7/IL-7R axis are evident, consistent with a process of immune exhaustion. IL-27 is an important immunoregulatory cytokine that shares T-cell signaling with IL-7 and other cytokines of the IL-12 family and might be involved in the transcriptional regulation of T-cell function. Here, we evaluated the expression and function of IL-27R in antigen-experienced T cells from subjects with chronic Chagas disease and assessed whether in vitro treatment with IL-27 and IL-7 might improve T. cruzi-specific polyfunctional T-cell responses. In vitro exposure of PBMCs to T. cruzi induced a downregulation of IL-27R in CD4+ T cells and an upregulation in CD8+ T cells in subjects without heart disease, while IL-27R expression remained unaltered in subjects with more severe clinical stages. The modulation of IL-27R was associated with functional signaling through STAT3 and STAT5 and induction of the downstream genes TBX21, EOMES and CXCL9 in response to IL-27. In vitro treatment of PBMCs with IL-27 and IL-7 improved monofunctional and polyfunctional Th1 responses, accompanied by the induction of IL-10 and Bcl-2 expression in subjects without heart disease but did not improve those in subjects with cardiomyopathy. Our findings support the process of desensitization of the IL-27/IL-27R pathway along with disease severity and that the pro-inflammatory and immunomodulatory mechanisms of IL-27 might be interconnected.
format	article
author	María Ailén Natale Todd Minning María Cecilia Albareda Melisa Daiana Castro Eiro María Gabriela Álvarez Bruno Lococo Gonzalo Cesar Graciela Bertocchi María Josefina Elias María Belén Caputo Rick Lee Tarleton Susana Adriana Laucella
author_facet	María Ailén Natale Todd Minning María Cecilia Albareda Melisa Daiana Castro Eiro María Gabriela Álvarez Bruno Lococo Gonzalo Cesar Graciela Bertocchi María Josefina Elias María Belén Caputo Rick Lee Tarleton Susana Adriana Laucella
author_sort	María Ailén Natale
title	Immune exhaustion in chronic Chagas disease: Pro-inflammatory and immunomodulatory action of IL-27 in vitro.
title_short	Immune exhaustion in chronic Chagas disease: Pro-inflammatory and immunomodulatory action of IL-27 in vitro.
title_full	Immune exhaustion in chronic Chagas disease: Pro-inflammatory and immunomodulatory action of IL-27 in vitro.
title_fullStr	Immune exhaustion in chronic Chagas disease: Pro-inflammatory and immunomodulatory action of IL-27 in vitro.
title_full_unstemmed	Immune exhaustion in chronic Chagas disease: Pro-inflammatory and immunomodulatory action of IL-27 in vitro.
title_sort	immune exhaustion in chronic chagas disease: pro-inflammatory and immunomodulatory action of il-27 in vitro.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/06691cc146b74fb197bcc2de737d9ef4
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Immune exhaustion in chronic Chagas disease: Pro-inflammatory and immunomodulatory action of IL-27 in vitro.

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