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Artículo

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

Somoza, MartínIcon ; Bertelli, AdrianoIcon ; Pratto, Cecilia A.; Verdun, Ramiro E.; Campetella, Oscar EduardoIcon ; Mucci, Juan SebastiánIcon
Fecha de publicación: 01/2022
Editorial: Frontiers Media
Revista: Frontiers in Cellular and Infection Microbiology
e-ISSN: 2235-2988
Idioma: Inglés
Tipo de recurso: Artículo publicado
Clasificación temática:
Enfermedades Infecciosas; Inmunología

Resumen

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 B220lo 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.
Palabras clave: B CELL PROLIFERATION , CHAGAS DISEASE , IL-21 , REGULATORY B CELLS , T CD4+ CELLS
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info:eu-repo/semantics/openAccess Excepto donde se diga explícitamente, este item se publica bajo la siguiente descripción: Creative Commons Attribution 2.5 Unported (CC BY 2.5)
Identificadores
URI: http://hdl.handle.net/11336/213498
URL: https://www.frontiersin.org/articles/10.3389/fcimb.2021.789373/full
DOI: http://dx.doi.org/10.3389/fcimb.2021.789373
Colecciones
Articulos (IIBIO)
Articulos de INSTITUTO DE INVESTIGACIONES BIOTECNOLOGICAS
Citación
Somoza, Martín; Bertelli, Adriano; Pratto, Cecilia A.; Verdun, Ramiro E.; Campetella, Oscar Eduardo; et al.; Trypanosoma cruzi Induces B Cells That Regulate the CD4+ T Cell Response; Frontiers Media; Frontiers in Cellular and Infection Microbiology; 11; 1-2022; 1-14
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