A participação do linfócito B na resposta imune protetora induzida pela infecção por Strongyloides venezuelensis em camundongo

Abstract

Strongyloidiasis is a chronicle parasitic disease that affects 30 to 100 million people in 70 countries worldwide. The development of the parasitic infection in asymptomatic or the potentially fatal disseminated form depends on the host immune response. Experimental and epidemiological evidences indicate that the development of type-2 immune response. In order to access the importance of the B- lymphocyte and antibodies in the immune response against Strongyloides venezuelensis, mice deficient in the production of IgM (MT-/-) and their wild type (WT) controls were comparatively evaluated during the primary and secondary infection by the nematode. The results demonstrate that parasite clearance was delayed in MT-/- infected mice during the primary and secondary infection. Although there was a delay in parasite elimination, MT-/- mice were able to control primary and secondary infection, suggesting that B-lymphocytes and/or antibodies participate in the protective mechanism against S. venezuelensis, but that they are not essential to this mechanism. In WT-/- infected mice, the serum concentration of IgE and L3-reactive IgM and IgG1 increased after 10 days of infection, coinciding with the parasite burden reduction. As expected, S. stercoralis infection did not induce IgM production in MT-/- mice, but in some infected deficient mice there was a small production of IgE and IgG1. The transference of serum immunoglobulins from WT to MT-/- mice at different points of S. venezuelensis infection restores the kinetics of worm elimination in deficient mice. These data indicate the participation of immunoglobulin in parasite clearance. We also evaluated the effect of the mice deficience on the establishment of the immune response induced by S. venezuelensis infection. Reduction of B-cell development in MT-/- mice was indirectly confirmed by the lower number of lymphocytes and higher proportion of CD4+ among the mesenteric lymph node cells from these mices. The absence of B-lymphocytes resulted in lower number of IL-4 producing lymphocytes in MLN, suggesting that B-cells are an important source of this cytokine in early infection. Moreover, the parasite infection in MT-/- mice induced higher number of INF- producing CD4+ cells and lower Treg cells in MNL, compared to WT-infected mice, but there was no difference in the total number of CD4+ cells producing IL-4 and IL-10 among the experimental groups. In the small intestine, the site of infection, the cytokine production was similar during early infection in both experimental groups. However, there was stronger cytokine production in MT-/- mice later on the infection and during the challenge, leading to a mixed Th-1/Th-2 immune response that interfered in the establishment of protective mechanisms. Moreover, MT-/- mice showed a lower Eosinophil Peroxidase and Myeloperoxidase activity in the sites of infection, suggesting a deficiency in the activation of these effector cells in absence of B-lymphocytes. In conclusion, our data confirmed that B-lymphocytes participate in the protective immune response against S. venezuelensis infection, possibly by antibody production and by modulation of immune response.