The Blockade of Interleukin-2 During the Acute Phase of Trypanosoma cruzi Infection Reveals Its Dominant Regulatory Role

Trypanosoma cruzi infection causes Chagas’ disease in humans. The infection activates the innate and adaptative immunity in an orchestrated immune response to control parasite growth, guaranteeing host survival. Despite an effective immune response to the parasite in the acute phase, the infection p...

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Autores principales:	Jorge Nihei, Fabiola Cardillo, Jose Mengel
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	Chagas’ disease Trypanosoma cruzi regulatory T cells anti-IL-2 interleukin-2 interleukin-10 Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/d1f0f58005fb4731bd7990b8b73e610a
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spelling	oai:doaj.org-article:d1f0f58005fb4731bd7990b8b73e610a2021-11-17T05:54:23ZThe Blockade of Interleukin-2 During the Acute Phase of Trypanosoma cruzi Infection Reveals Its Dominant Regulatory Role2235-298810.3389/fcimb.2021.758273https://doaj.org/article/d1f0f58005fb4731bd7990b8b73e610a2021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fcimb.2021.758273/fullhttps://doaj.org/toc/2235-2988Trypanosoma cruzi infection causes Chagas’ disease in humans. The infection activates the innate and adaptative immunity in an orchestrated immune response to control parasite growth, guaranteeing host survival. Despite an effective immune response to the parasite in the acute phase, the infection progresses to a chronic stage. The parasite infects different tissues such as peripheral neurons, the brain, skeletal muscle, and heart muscle, among many others. It is evident now that tissue-specific immune responses may develop along with anti-parasite immunity. Therefore, mechanisms to regulate immunity and to ensure tissue-specific tolerance are operating during the infection. Studying those immunoregulatory mechanisms is fundamental to improve host protection or control inflammatory reactions that may lead to pathology. The role of IL-2 during T. cruzi infection is not established. IL-2 production by T cells is strongly down-modulated early in the disease by unknown mechanisms and remains low during the chronic phase of the disease. IL-2 activates NK cells, CD4, and CD8 T cells and may be necessary to immunity development. Also, the expansion and maintenance of regulatory T cells require IL-2. Thus, IL-2 may be a key cytokine involved in promoting or down-regulating immune responses, probably in a dose-dependent manner. This study blocked IL-2 during the acute T. cruzi infection by using a neutralizing monoclonal antibody. The results show that parasitemia and mortality rate was lower in animals treated with anti-IL-2. The percentages and total numbers of CD4+CD25+Foxp3+ T cells diminished within three weeks of infection. The numbers of splenic activated/memory CD4 and CD8 splenic T cells increased during the acute infection. T cells producing IFN-γ, TNF-α and IL-10 also augmented in anti-IL-2-treated infected mice. The IL-2 blockade also increased the numbers of inflammatory cells in the heart and skeletal muscles and the amount of IL-17 produced by heart T cells. These results suggest that IL-2 might be involved in the immune regulatory response during the acute T. cruzi infection, dampening T cell activation through the expansion/maintenance of regulatory T cells and regulating IL-17 production. Therefore, the IL-2 pathway is an attractive target for therapeutic purposes in acute and chronic phases of Chagas’ disease.Jorge NiheiJorge NiheiFabiola CardilloJose MengelJose MengelFrontiers Media S.A.articleChagas’ diseaseTrypanosoma cruziregulatory T cellsanti-IL-2interleukin-2interleukin-10MicrobiologyQR1-502ENFrontiers in Cellular and Infection Microbiology, Vol 11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Chagas’ disease Trypanosoma cruzi regulatory T cells anti-IL-2 interleukin-2 interleukin-10 Microbiology QR1-502
spellingShingle	Chagas’ disease Trypanosoma cruzi regulatory T cells anti-IL-2 interleukin-2 interleukin-10 Microbiology QR1-502 Jorge Nihei Jorge Nihei Fabiola Cardillo Jose Mengel Jose Mengel The Blockade of Interleukin-2 During the Acute Phase of Trypanosoma cruzi Infection Reveals Its Dominant Regulatory Role
description	Trypanosoma cruzi infection causes Chagas’ disease in humans. The infection activates the innate and adaptative immunity in an orchestrated immune response to control parasite growth, guaranteeing host survival. Despite an effective immune response to the parasite in the acute phase, the infection progresses to a chronic stage. The parasite infects different tissues such as peripheral neurons, the brain, skeletal muscle, and heart muscle, among many others. It is evident now that tissue-specific immune responses may develop along with anti-parasite immunity. Therefore, mechanisms to regulate immunity and to ensure tissue-specific tolerance are operating during the infection. Studying those immunoregulatory mechanisms is fundamental to improve host protection or control inflammatory reactions that may lead to pathology. The role of IL-2 during T. cruzi infection is not established. IL-2 production by T cells is strongly down-modulated early in the disease by unknown mechanisms and remains low during the chronic phase of the disease. IL-2 activates NK cells, CD4, and CD8 T cells and may be necessary to immunity development. Also, the expansion and maintenance of regulatory T cells require IL-2. Thus, IL-2 may be a key cytokine involved in promoting or down-regulating immune responses, probably in a dose-dependent manner. This study blocked IL-2 during the acute T. cruzi infection by using a neutralizing monoclonal antibody. The results show that parasitemia and mortality rate was lower in animals treated with anti-IL-2. The percentages and total numbers of CD4+CD25+Foxp3+ T cells diminished within three weeks of infection. The numbers of splenic activated/memory CD4 and CD8 splenic T cells increased during the acute infection. T cells producing IFN-γ, TNF-α and IL-10 also augmented in anti-IL-2-treated infected mice. The IL-2 blockade also increased the numbers of inflammatory cells in the heart and skeletal muscles and the amount of IL-17 produced by heart T cells. These results suggest that IL-2 might be involved in the immune regulatory response during the acute T. cruzi infection, dampening T cell activation through the expansion/maintenance of regulatory T cells and regulating IL-17 production. Therefore, the IL-2 pathway is an attractive target for therapeutic purposes in acute and chronic phases of Chagas’ disease.
format	article
author	Jorge Nihei Jorge Nihei Fabiola Cardillo Jose Mengel Jose Mengel
author_facet	Jorge Nihei Jorge Nihei Fabiola Cardillo Jose Mengel Jose Mengel
author_sort	Jorge Nihei
title	The Blockade of Interleukin-2 During the Acute Phase of Trypanosoma cruzi Infection Reveals Its Dominant Regulatory Role
title_short	The Blockade of Interleukin-2 During the Acute Phase of Trypanosoma cruzi Infection Reveals Its Dominant Regulatory Role
title_full	The Blockade of Interleukin-2 During the Acute Phase of Trypanosoma cruzi Infection Reveals Its Dominant Regulatory Role
title_fullStr	The Blockade of Interleukin-2 During the Acute Phase of Trypanosoma cruzi Infection Reveals Its Dominant Regulatory Role
title_full_unstemmed	The Blockade of Interleukin-2 During the Acute Phase of Trypanosoma cruzi Infection Reveals Its Dominant Regulatory Role
title_sort	blockade of interleukin-2 during the acute phase of trypanosoma cruzi infection reveals its dominant regulatory role
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/d1f0f58005fb4731bd7990b8b73e610a
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The Blockade of Interleukin-2 During the Acute Phase of Trypanosoma cruzi Infection Reveals Its Dominant Regulatory Role

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