B cells modulate T cells so as to favour T helper type 1 and CD8⁺ T‐cell responses in the acute phase of Trypanosoma cruzi infection

Abstract

Summary In this study, we have evaluated the production of pro‐ and anti‐inflammatory cytokines and the formation of central and effector memory T cells in mice lacking mature B cells (muMT KO). The results show that Trypanosoma cruzi infection in C57Bl/6mμ MT KO mice is intensified in relation to control mice and this exacerbation is related to low levels of inflammatory cytokines produced during the acute infection and the lower numbers of central and effector memory CD4+ and CD8+ T cells generated during the acute phase of the infection. In addition, a marked reduction in the CD8+ T‐cell subpopulation was observed in muMT KO infected mice. In agreement to this, the degree of tissue parasitism was increased in muMT mice and the tissue inflammatory response was much less intense in the acute phase of the infection, consistent with a deficit in the generation of effector T cells. Flow cytometry analysis of the skeletal muscle inflammatory infiltrate showed a predominance of CD8+ CD45Rb low in B‐cell‐sufficient C57Bl/6 mice, whereas the preponderant cell type in muMT KO skeletal muscle inflammatory infiltrate was CD4+ T cells. In addition, CD8+ T cells found in skeletal muscle from muMT KO infected mice were less activated than in control B‐cell sufficient infected mice. These results suggest that B cells may participate in the generation of effector/memory T cells. In addition and more importantly, B cells were crucial in the maintenance of central and effector memory CD8+ T cell, as well as the determination of the T cell cytokine functional pattern, and they may therefore account for critical aspects of the resistance to intracellular pathogens, such as T. cruzi.

Modulation of immune response in experimental Chagas disease

“…As a result of this process, regulation of the cellular response occurs due to a reduction in the activation of dendritic cells and in the macrophage's microbicidal activity. In addition, IL-4 takes part in inducing transforming growth factor (TGF)β which regulates the activity of the antigen presenting cells and enhance the susceptibility of infection by T. cruzi [32] . In this sense, we observed in our experimental model [31,33] (n = 6 for each group and each experiment performed) that vaccinated animals had a significant increase of IL-12, down regulation of the proinflammatory cytokines, IL-6, IFNγ, TNFα, and increase of soluble TNF receptors sTNFIR and sTNFIIR, which inhibit the deletereous activity of TNFα, in accord with Camargo et al [27] .…”

“…As it was above mentioned, both types of cells secrete IFNγ, which activates the macrophage in order to exert trypanosomicide activity by means of NO. Antigen presenting cells like macrophages, dendritic cells and B lymphocytes play an essential role in generating effector T lymphocytes, which produce different cytokines involved in the polarization of the TH1 or TH2 immune response [32] . Despite this, T. cruzi is capable of surviving in the host for long periods, which contributes to the development of symptoms and chronic disease [54] .…”

The Interleukin-17 (IL-17) puzzle in Chagas disease

“…During the acute phase, an effective immune response is settled to control parasite replication in the tissues [5] . NK, T, and B cells are crucial to mediate parasite clearance through the production of interferon-γ, interleukin-17 and specific antibodies [4][5][6][7] . Immunity cannot sterilize the host, thus leading to infection persistence and therefore, a chronic disease [5] .…”

Avaliação das perspectivas terapêuticas do ácido L-tiazolidina-4-carboxílico, um análogo de prolina, na infecção de camundongos pelo Trypanosoma cruzi.

“…Outro componente importante da imunidade inata são as células Natural Killers. Além de lisarem diretamente as células infectadas, as NKs são capazes de produzir enormes quantidades de IFN-γ, principalmente no fígado de camundongos durante a fase aguda da infecção, o que é consequência da produção de IL-12 e TNF-α pelas células dendríticas e macrófagos (Golgher e Gazzinelli, 2004;Sardinha et al, 2006;Cardillo et al, 2007).…”