Trypanosoma cruzi trans-sialidase prevents elicitation of Th1 cell response via interleukin 10 and downregulates Th1 effector cells

The trans-sialidases (TSs) from Trypanosoma cruzi, the agent of Chagas disease, are virulence factors shed to the bloodstream that induce strong alterations in the immune system. Here, we report that both enzymatically active TS (aTS) and its lectinlike isoform (iTS) disturb CD4 T cell physiology, i...

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Autores principales:	Musikant, Alejandro Daniel, Leguizamón, María Susana, Campetella, Oscar Eduardo
Publicado:	2015
Materias:	gamma interferon interleukin 10 interleukin 2 interleukin 4 neutralizing antibody ovalbumin protein kinase ZAP 70 sialidase T lymphocyte receptor trans sialidase unclassified drug glycoprotein immunologic factor trans-sialidase virulence factor animal cell animal experiment antigen presenting cell Article CD4+ T lymphocyte cell expansion cell interaction cell stimulation cell survival clone controlled study cytokine production cytokine release down regulation effector cell enzyme activity in vivo study male mouse nonhuman parasite survival phenotype polarization priority journal protein expression Th1 cell Trypanosoma cruzi upregulation animal Bagg albino mouse immune evasion immunology metabolism secretion (process) Animals Glycoproteins Immune Evasion Immunologic Factors Interferon-gamma Interleukin-10 Interleukin-2 Interleukin-4 Male Mice, Inbred BALB C Neuraminidase Th1 Cells Virulence Factors
Acceso en línea:	https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00199567_v83_n5_p2099_Diaz http://hdl.handle.net/20.500.12110/paper_00199567_v83_n5_p2099_Diaz
Aporte de:	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) de Universidad de Buenos Aires

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spelling	paper:paper_00199567_v83_n5_p2099_Diaz2023-06-08T14:40:19Z Trypanosoma cruzi trans-sialidase prevents elicitation of Th1 cell response via interleukin 10 and downregulates Th1 effector cells Musikant, Alejandro Daniel Leguizamón, María Susana Campetella, Oscar Eduardo gamma interferon interleukin 10 interleukin 2 interleukin 4 neutralizing antibody ovalbumin protein kinase ZAP 70 sialidase T lymphocyte receptor trans sialidase unclassified drug gamma interferon glycoprotein immunologic factor interleukin 10 interleukin 2 interleukin 4 sialidase trans-sialidase virulence factor animal cell animal experiment antigen presenting cell Article CD4+ T lymphocyte cell expansion cell interaction cell stimulation cell survival clone controlled study cytokine production cytokine release down regulation effector cell enzyme activity in vivo study male mouse nonhuman parasite survival phenotype polarization priority journal protein expression Th1 cell Trypanosoma cruzi upregulation animal Bagg albino mouse immune evasion immunology metabolism secretion (process) Th1 cell Trypanosoma cruzi Animals Glycoproteins Immune Evasion Immunologic Factors Interferon-gamma Interleukin-10 Interleukin-2 Interleukin-4 Male Mice, Inbred BALB C Neuraminidase Th1 Cells Trypanosoma cruzi Virulence Factors The trans-sialidases (TSs) from Trypanosoma cruzi, the agent of Chagas disease, are virulence factors shed to the bloodstream that induce strong alterations in the immune system. Here, we report that both enzymatically active TS (aTS) and its lectinlike isoform (iTS) disturb CD4 T cell physiology, inducing downregulation of Th1 cell functionality and in vivo cell expansion. By using ovalbumin-specific DO11.10 cells as tracers of clones developing the Th1 phenotype, we found that the infection induced significant amounts of gamma interferon (IFN-γ) but low levels of interleukin 2 (IL-2) and increased IL-4 production in vivo, in agreement with a mixed T helper response. The production of cytokines associated with the Th2 phenotype was prevented by passive transfer of anti-TS neutralizing antibodies. TSs also reduced the T cell receptor signaling as assayed by Zap-70 phosphorylation. TSs also reduced IL-2 and IFN-γ secretion, with a concomitant increase in IL-4 production and then an unbalancing of the CD4 T cell response toward the Th2 phenotype. This effect was prevented by using anti-IL-10 neutralizing antibodies or IL-10-/- antigen-presenting cells, supporting the subversion of this regulatory pathway. In support, TSs stimulated IL-10 secretion by antigen-presenting cells during their interaction with CD4 T cells. When polarized cells were stimulated in the presence of TSs, the secretion of IL-2 and IFN-γ was strongly downregulated in Th1 cells, while IL-2 production was upregulated in Th2 cells. Although the Th1 response is associated with host survival, it may simultaneously induce extensive damage to infected tissues. Thus, by delaying the elicitation of the Th1 response and limiting its effector properties, TSs restrain the cell response, supporting T. cruzi colonization and persistence while favoring host survival. © 2015, American Society for Microbiology. Fil:Musikant, D. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Leguizamón, M.S. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Campetella, O. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. 2015 https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00199567_v83_n5_p2099_Diaz http://hdl.handle.net/20.500.12110/paper_00199567_v83_n5_p2099_Diaz
institution	Universidad de Buenos Aires
institution_str	I-28
repository_str	R-134
collection	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA)
topic	gamma interferon interleukin 10 interleukin 2 interleukin 4 neutralizing antibody ovalbumin protein kinase ZAP 70 sialidase T lymphocyte receptor trans sialidase unclassified drug gamma interferon glycoprotein immunologic factor interleukin 10 interleukin 2 interleukin 4 sialidase trans-sialidase virulence factor animal cell animal experiment antigen presenting cell Article CD4+ T lymphocyte cell expansion cell interaction cell stimulation cell survival clone controlled study cytokine production cytokine release down regulation effector cell enzyme activity in vivo study male mouse nonhuman parasite survival phenotype polarization priority journal protein expression Th1 cell Trypanosoma cruzi upregulation animal Bagg albino mouse immune evasion immunology metabolism secretion (process) Th1 cell Trypanosoma cruzi Animals Glycoproteins Immune Evasion Immunologic Factors Interferon-gamma Interleukin-10 Interleukin-2 Interleukin-4 Male Mice, Inbred BALB C Neuraminidase Th1 Cells Trypanosoma cruzi Virulence Factors
spellingShingle	gamma interferon interleukin 10 interleukin 2 interleukin 4 neutralizing antibody ovalbumin protein kinase ZAP 70 sialidase T lymphocyte receptor trans sialidase unclassified drug gamma interferon glycoprotein immunologic factor interleukin 10 interleukin 2 interleukin 4 sialidase trans-sialidase virulence factor animal cell animal experiment antigen presenting cell Article CD4+ T lymphocyte cell expansion cell interaction cell stimulation cell survival clone controlled study cytokine production cytokine release down regulation effector cell enzyme activity in vivo study male mouse nonhuman parasite survival phenotype polarization priority journal protein expression Th1 cell Trypanosoma cruzi upregulation animal Bagg albino mouse immune evasion immunology metabolism secretion (process) Th1 cell Trypanosoma cruzi Animals Glycoproteins Immune Evasion Immunologic Factors Interferon-gamma Interleukin-10 Interleukin-2 Interleukin-4 Male Mice, Inbred BALB C Neuraminidase Th1 Cells Trypanosoma cruzi Virulence Factors Musikant, Alejandro Daniel Leguizamón, María Susana Campetella, Oscar Eduardo Trypanosoma cruzi trans-sialidase prevents elicitation of Th1 cell response via interleukin 10 and downregulates Th1 effector cells
topic_facet	gamma interferon interleukin 10 interleukin 2 interleukin 4 neutralizing antibody ovalbumin protein kinase ZAP 70 sialidase T lymphocyte receptor trans sialidase unclassified drug gamma interferon glycoprotein immunologic factor interleukin 10 interleukin 2 interleukin 4 sialidase trans-sialidase virulence factor animal cell animal experiment antigen presenting cell Article CD4+ T lymphocyte cell expansion cell interaction cell stimulation cell survival clone controlled study cytokine production cytokine release down regulation effector cell enzyme activity in vivo study male mouse nonhuman parasite survival phenotype polarization priority journal protein expression Th1 cell Trypanosoma cruzi upregulation animal Bagg albino mouse immune evasion immunology metabolism secretion (process) Th1 cell Trypanosoma cruzi Animals Glycoproteins Immune Evasion Immunologic Factors Interferon-gamma Interleukin-10 Interleukin-2 Interleukin-4 Male Mice, Inbred BALB C Neuraminidase Th1 Cells Trypanosoma cruzi Virulence Factors
description	The trans-sialidases (TSs) from Trypanosoma cruzi, the agent of Chagas disease, are virulence factors shed to the bloodstream that induce strong alterations in the immune system. Here, we report that both enzymatically active TS (aTS) and its lectinlike isoform (iTS) disturb CD4 T cell physiology, inducing downregulation of Th1 cell functionality and in vivo cell expansion. By using ovalbumin-specific DO11.10 cells as tracers of clones developing the Th1 phenotype, we found that the infection induced significant amounts of gamma interferon (IFN-γ) but low levels of interleukin 2 (IL-2) and increased IL-4 production in vivo, in agreement with a mixed T helper response. The production of cytokines associated with the Th2 phenotype was prevented by passive transfer of anti-TS neutralizing antibodies. TSs also reduced the T cell receptor signaling as assayed by Zap-70 phosphorylation. TSs also reduced IL-2 and IFN-γ secretion, with a concomitant increase in IL-4 production and then an unbalancing of the CD4 T cell response toward the Th2 phenotype. This effect was prevented by using anti-IL-10 neutralizing antibodies or IL-10-/- antigen-presenting cells, supporting the subversion of this regulatory pathway. In support, TSs stimulated IL-10 secretion by antigen-presenting cells during their interaction with CD4 T cells. When polarized cells were stimulated in the presence of TSs, the secretion of IL-2 and IFN-γ was strongly downregulated in Th1 cells, while IL-2 production was upregulated in Th2 cells. Although the Th1 response is associated with host survival, it may simultaneously induce extensive damage to infected tissues. Thus, by delaying the elicitation of the Th1 response and limiting its effector properties, TSs restrain the cell response, supporting T. cruzi colonization and persistence while favoring host survival. © 2015, American Society for Microbiology.
author	Musikant, Alejandro Daniel Leguizamón, María Susana Campetella, Oscar Eduardo
author_facet	Musikant, Alejandro Daniel Leguizamón, María Susana Campetella, Oscar Eduardo
author_sort	Musikant, Alejandro Daniel
title	Trypanosoma cruzi trans-sialidase prevents elicitation of Th1 cell response via interleukin 10 and downregulates Th1 effector cells
title_short	Trypanosoma cruzi trans-sialidase prevents elicitation of Th1 cell response via interleukin 10 and downregulates Th1 effector cells
title_full	Trypanosoma cruzi trans-sialidase prevents elicitation of Th1 cell response via interleukin 10 and downregulates Th1 effector cells
title_fullStr	Trypanosoma cruzi trans-sialidase prevents elicitation of Th1 cell response via interleukin 10 and downregulates Th1 effector cells
title_full_unstemmed	Trypanosoma cruzi trans-sialidase prevents elicitation of Th1 cell response via interleukin 10 and downregulates Th1 effector cells
title_sort	trypanosoma cruzi trans-sialidase prevents elicitation of th1 cell response via interleukin 10 and downregulates th1 effector cells
publishDate	2015
url	https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00199567_v83_n5_p2099_Diaz http://hdl.handle.net/20.500.12110/paper_00199567_v83_n5_p2099_Diaz
work_keys_str_mv	AT musikantalejandrodaniel trypanosomacruzitranssialidasepreventselicitationofth1cellresponseviainterleukin10anddownregulatesth1effectorcells AT leguizamonmariasusana trypanosomacruzitranssialidasepreventselicitationofth1cellresponseviainterleukin10anddownregulatesth1effectorcells AT campetellaoscareduardo trypanosomacruzitranssialidasepreventselicitationofth1cellresponseviainterleukin10anddownregulatesth1effectorcells
_version_	1768544440050253824

Trypanosoma cruzi trans-sialidase prevents elicitation of Th1 cell response via interleukin 10 and downregulates Th1 effector cells

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