MicroRNA-155 contributes to host immunity against Toxoplasma gondii

Toxoplasma gondii is well known to infect almost all avian and mammalian species including humans, with worldwide distribution. This protozoan parasite can cause serious toxoplasmosis, posing with a risk to public health. The role of microRNAs in the pathogenesis of T. gondii has not been well described. The aim 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 in mice models. The survival and parasite burden in T. gondii-infected miR-155^-/- and wild-type (WT) C57BL6 mice were compared. In these two mouse models, ELISA tests were used for analysis of Th1-associated, Th2-associated, and Th17-associated cytokines, and flow cytometry was used for analysis of the subpopulations of NK, NKT, CD8⁺T, CD4⁺T cells and regulatory T cells (Tregs), as well as Ly6Chi inflammatory monocytes and dendritic cells. 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, along with decreased proinflammatory mediators, Th-1-associated and Th-2-associated cytokines and accumulation of lymphocyte subpopulations. Also, CD8⁺ T cell exhaustion was also worsened in the absence of miR-155 via targeting of SHIP-1 and SOCS1, showing as up-regulated recruitment of Tregs and expression of PD-1, and down-regulated expression of IFN-γ and TNF-α in CD8⁺ T cells. Our results show that miR-155 is a critical immune regulator for the control of T. gondii infection, suggesting that miR-155 can be explored as a potential molecular target for boosting immunity against T. gondii.