Dados do Trabalho

Título

Schitosoma mansoni infection increases the frequency of regulatory CD4 + T lymphocytes by IL-10, TGF-β, and PD-1 pathways

Introdução

Schistosoma mansoni infections are associated with polarization of type 2 immune response. Furthermore, these helminths exploit immunoregulatory pathways as a survival mechanism. Regulatory CD4+ T lymphocytes are known to participate in this response

Objetivo (s)

We aimed to analyze the regulatory signature mediated by T reg lymphocytes from individuals infected with S. mansoni.

Material e Métodos

Of the 17 participants, 10 (59%) had S. mansoni infection and 7 (41%) had no infection. Regulatory lymphocytes were obtained from PBMC and stimulated with the S. mansoni egg antigen (SEA) to phenotypic and intracellular cytokine evaluation performed by flow cytometry. T reg cells were then isolated with magnetic beads for use in T reg lymphocyte-depleted cultures. In these cultures, the levels of IL-10, IL-13, Il-17 and IFN-γ were evaluated by ELISA.

Resultados e Conclusão

We observed higher frequencies of Treg lymphocytes (TCD4+ CD25+ FoxP3+), as well as higher expression of IL-10 and TGF-β by these cells. It was also observed in infected individuals a higher frequency of CD4+CD25+FoxP3+PD-1+ T cells, while there was no difference in the expression of CTLA-4 by these lymphocytes. Increased PD-1 and TGF-β expression were also observed in non-regulatory T lymphocyte populations (CD4+CD25LowFOXP3neg) suggesting that in chronic schistosomiasis some regulatory pathways may not be exclusive to T reg populations. Individuals infected with S. mansoni have higher levels of IL-10 and IL-13 in the PBMC supernatant cultures and lower levels of IFN- compared to non-infected individuals. T reg cell depletion led to a reduction of IL-10 and IL-13 levels, whereas it did not alter IFN- levels in the group of infected individuals. In individuals infected with S. mansoni the regulatory mechanisms seem to involve IL-10, TGF-β, and PD-1 pathways, but not CTLA-4. Additionally, the expression of TGF-β, PD-1, is not restricted to regulatory populations. These data contribute to increase our knowledge of the pathways explored by these parasites favoring the survival of S. mansoni.

Palavras-chave

Regulatory CD4+ T lymphocytes; Schistosoma mansoni; schistosomiasis.

Agradecimentos

CNPq/MST/INCT-DT, FAPESB, Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - Brasil (CAPES)