MicroRNA-155 Deficiency Exacerbates Trypanosoma cruzi Infection

Abstract

Chagas disease, caused by the intracellular protozoan parasite Trypanosoma cruzi, is a public health problem affecting 6 to 8 million people, mainly in Latin America. The role of microRNAs in the pathogenesis of Chagas disease has not been well described. Here, we investigate the role of microRNA-155 (miR-155), a proinflammatory host innate immune regulator responsible for T helper type 1 and type 17 (Th1 and Th17) development and macrophage responses during T. cruzi infection. For this, we compared the survival and parasite growth and distribution in miR-155−/− and wild-type (WT) C57BL/6 mice. The lack of miR-155 caused robust parasite infection and diminished survival of infected mice, while WT mice were resistant to infection. Immunological analysis of infected mice indicated that, in the absence of miR-155, there was decreased interferon gamma (IFN-γ) and tumor necrosis factor alpha (TNF-α) production. In addition, we found that there was a significant reduction of CD8-positive (CD8+) T cells, natural killer (NK) cells, and NK-T cells and increased accumulation of neutrophils and inflammatory monocytes in miR-155−/− mice. Collectively, these data indicate that miR-155 is an important immune regulatory molecule critical for the control of T. cruzi infection.

MicroRNA 155 Contributes to Host Immunity Against Toxoplasm Gondii

“…Our studies have shown decreased accumulation of Ly6C + in ammatory monocytes and DCs in miR155KO mice, associated with a signi cantly increased parasite load and with the reduced expression of those proin ammatory mediators. However, it is contradictory that aberrant miR-155 expression has recently been shown to adversely affect Ly6C + in ammatory monocytes migration in L. donovani and T. cruzi, which is due to a fact that in ammatory monocytes facilitate the growth of the parasites in the spleen in visceral leishmaniasis and trypanosomosis [16,17]. These results demonstrate that miR155 de ciency exacerbated T. gondii infection through the down-regulation of DCs and in ammatory monocyte in ltration.…”

“…As miR-155 has been shown to be critical for regulating T cell responses as well as in ammatory responses and cytokine signals, which have the well-documented roles in the control of intracellular pathogens, including T. cruzi and Leishmania donovani [16,17], we further analyzed the production of cytokines Th1-associated IFN-γ, IL-2, Th2-associated IL-4 and IL-13, Th17-associated IL-17A and IL-17F by splenic cells harvested from WT and miR155KO (miR-155 −/− ) mice after infection with T. gonii PRU cysts.…”

“…MiR-155 has recently been uncovered to be contributed to the resistance to the experimental parasitic diseases [16,17]. To test if the lack of miR-155 would potentiate the chronic T. gondii in mice models, miR-155 −/− mice were orally inoculated with 10 PRU tissue cysts.…”

“…MiR-155 regulates the activation of several immune subpopulations including CD8 + T cells, as well as NK and NKT cells [34,35], which is critical for immunity against T. gondii infection [31]. Previous studies have found that miR-155 is important in control of the Leishmania donovani and T. cruzi infection by mediating the regulation of T-cell proliferation and thus the activation of CD8 + T cells, NK and NKT cells [16,17]. In support with these studies, our data indicate that those decreased recruitment of CD8 + T cells, NK and NKT cells resulting from the absence of miR-155 expression, can lead to the lack of control of parasite infection in the miR-155 −/− mice.…”

“…MiR-155 has a regulative role in visceral leishmaniasis by up-regulating of both Th1 and Th2 immune responses, which is contributed to the control of the infection [16]. has been demonstrated to be an important immune regulatory molecule critical for the control of Trypanosoma cruzi infection [17]. Likewise, miR-155 is ascertained to play a critical role in maintaining the survival of Mtb-infected macrophages and the function of Mtb-speci c T-cells during Mycobacterium tuberculosis infection [18].…”