Abstract
Background: Toxoplasma gondii is known to infect almost all the mammalian including human beings and avian species, with worldwide distribution, and cause serious toxoplasmosis, posing regards with public health problem. The role of microRNAs in the pathogenesis of T. gondii has not been well described. The objective of the present study was to investigate the role of microRNA-155 (miR-155) in mediating innate and adaptive immune responses during T. gondii infection. Methods: The survival and parasite burden in T. gondii-infected miR-155-/- and WT C57BL6 mice were compared. In these two mouse models, ELISA were used for analysis of Th1-associated, Th-2 associated, and Th-17 associated cytokines, and flow cytometry were used for analysis of the subpopulations of NK, NKT, CD8+T, CD4+T cells and Tregs, as well as Ly6Chi inflammatory monocytes and DCs. Proinflammatory mediators and CD8+ T cells responses were also analyzed by using qRT-PCR and flow cytometry, respectively. In the end, the expression of the direct target of miR-155, SHIP-1 and SOCS1 was analyzed by using qRT-PCR.Results: The lack of miR-155 led to increased parasite burden and decreased survival of infected mice in contrast to WT mice. Innate and adaptive immune responses were reduced in the absence of miR-155, associated with diminished Proinflammatory mediators, Th1-associated and Th-2 associated cytokines and accumulation of lymphocyte subpopulations. Also, CD8+ T cells exhaustion was also worsened in the absence of miR-155 via targeting to SHIP-1 and SOCS1, showing as up-regulated recruit of Tregs and expression of PD-1 and, and down-regulated expression of IFN-γ and TNF-α in CD8+ T cells.Conclusion: miR-155 is a critical immune regulator for the control of T. gondii infection, suggesting that miR155 can be explored as a potential molecular target for boosting immunity against T. gondii.
Suppression of host adaptive immune responses by Neisseria gonorrhoeae: role of interleukin 10 and type 1 regulatory T cells