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Trypanosoma cruzi Induces B Cells That Regulate the CD4(+) T Cell Response

Trypanosoma cruzi infection induces a polyclonal B cell proliferative response characterized by maturation to plasma cells, excessive generation of germinal centers, and secretion of parasite-unrelated antibodies. Although traditionally reduced to the humoral response, several infectious and non-inf...

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Autores principales: Somoza, Martín, Bertelli, Adriano, Pratto, Cecilia A., Verdun, Ramiro E., Campetella, Oscar, Mucci, Juan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8766854/
https://www.ncbi.nlm.nih.gov/pubmed/35071041
http://dx.doi.org/10.3389/fcimb.2021.789373
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author Somoza, Martín
Bertelli, Adriano
Pratto, Cecilia A.
Verdun, Ramiro E.
Campetella, Oscar
Mucci, Juan
author_facet Somoza, Martín
Bertelli, Adriano
Pratto, Cecilia A.
Verdun, Ramiro E.
Campetella, Oscar
Mucci, Juan
author_sort Somoza, Martín
collection PubMed
description Trypanosoma cruzi infection induces a polyclonal B cell proliferative response characterized by maturation to plasma cells, excessive generation of germinal centers, and secretion of parasite-unrelated antibodies. Although traditionally reduced to the humoral response, several infectious and non-infectious models revealed that B lymphocytes could regulate and play crucial roles in cellular responses. Here, we analyze the trypomastigote-induced effect on B cells, their effects on CD4(+) T cells, and their correlation with in vivo findings. The trypomastigotes were able to induce the proliferation and the production of IL-10 or IL-6 of naïve B cells in co-culture experiments. Also, we found that IL-10-producing B220(lo) cells were elicited in vivo. We also found up-regulated expression of FasL and PD-L1, proteins involved in apoptosis induction and inhibition of TCR signaling, and of BAFF and APRIL mRNAs, two B-cell growth factors. Interestingly, it was observed that IL-21, which plays a critical role in regulatory B cell differentiation, was significantly increased in B220(+)/IL-21(+) in in vivo infections. This is striking since the secretion of IL-21 is associated with T helper follicular cells. Furthermore, trypomastigote-stimulated B-cell conditioned medium dramatically reduced the proliferation and increased the apoptotic rate on CD3/CD28 activated CD4(+) T cells, suggesting the development of effective regulatory B cells. In this condition, CD4(+) T cells showed a marked decrease in proliferation and viability with marginal IL-2 or IFNγ secretion, which is counterproductive with an efficient immune response against T. cruzi. Altogether, our results show that B lymphocytes stimulated with trypomastigotes adopt a particular phenotype that exerts a strong regulation of this T cell compartment by inducing apoptosis, arresting cell division, and affecting the developing of a proinflammatory response.
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spelling pubmed-87668542022-01-20 Trypanosoma cruzi Induces B Cells That Regulate the CD4(+) T Cell Response Somoza, Martín Bertelli, Adriano Pratto, Cecilia A. Verdun, Ramiro E. Campetella, Oscar Mucci, Juan Front Cell Infect Microbiol Cellular and Infection Microbiology Trypanosoma cruzi infection induces a polyclonal B cell proliferative response characterized by maturation to plasma cells, excessive generation of germinal centers, and secretion of parasite-unrelated antibodies. Although traditionally reduced to the humoral response, several infectious and non-infectious models revealed that B lymphocytes could regulate and play crucial roles in cellular responses. Here, we analyze the trypomastigote-induced effect on B cells, their effects on CD4(+) T cells, and their correlation with in vivo findings. The trypomastigotes were able to induce the proliferation and the production of IL-10 or IL-6 of naïve B cells in co-culture experiments. Also, we found that IL-10-producing B220(lo) cells were elicited in vivo. We also found up-regulated expression of FasL and PD-L1, proteins involved in apoptosis induction and inhibition of TCR signaling, and of BAFF and APRIL mRNAs, two B-cell growth factors. Interestingly, it was observed that IL-21, which plays a critical role in regulatory B cell differentiation, was significantly increased in B220(+)/IL-21(+) in in vivo infections. This is striking since the secretion of IL-21 is associated with T helper follicular cells. Furthermore, trypomastigote-stimulated B-cell conditioned medium dramatically reduced the proliferation and increased the apoptotic rate on CD3/CD28 activated CD4(+) T cells, suggesting the development of effective regulatory B cells. In this condition, CD4(+) T cells showed a marked decrease in proliferation and viability with marginal IL-2 or IFNγ secretion, which is counterproductive with an efficient immune response against T. cruzi. Altogether, our results show that B lymphocytes stimulated with trypomastigotes adopt a particular phenotype that exerts a strong regulation of this T cell compartment by inducing apoptosis, arresting cell division, and affecting the developing of a proinflammatory response. Frontiers Media S.A. 2022-01-05 /pmc/articles/PMC8766854/ /pubmed/35071041 http://dx.doi.org/10.3389/fcimb.2021.789373 Text en Copyright © 2022 Somoza, Bertelli, Pratto, Verdun, Campetella and Mucci https://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) and the copyright owner(s) 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 Cellular and Infection Microbiology
Somoza, Martín
Bertelli, Adriano
Pratto, Cecilia A.
Verdun, Ramiro E.
Campetella, Oscar
Mucci, Juan
Trypanosoma cruzi Induces B Cells That Regulate the CD4(+) T Cell Response
title Trypanosoma cruzi Induces B Cells That Regulate the CD4(+) T Cell Response
title_full Trypanosoma cruzi Induces B Cells That Regulate the CD4(+) T Cell Response
title_fullStr Trypanosoma cruzi Induces B Cells That Regulate the CD4(+) T Cell Response
title_full_unstemmed Trypanosoma cruzi Induces B Cells That Regulate the CD4(+) T Cell Response
title_short Trypanosoma cruzi Induces B Cells That Regulate the CD4(+) T Cell Response
title_sort trypanosoma cruzi induces b cells that regulate the cd4(+) t cell response
topic Cellular and Infection Microbiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8766854/
https://www.ncbi.nlm.nih.gov/pubmed/35071041
http://dx.doi.org/10.3389/fcimb.2021.789373
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