TLR4 receptor is involved in the expansion of hepatic monocytic myeloid suppressor cells and implicated in the severity of acute infection with Trypanosoma cruzi

Buenos Aires

Congreso; Meeting of the Argentinian Immunology Society; 2015

Sociedad Argentina de Inmunología

Background: We previously demonstrated that myeloid-derived suppressor cells (MDSCs) are key players in the resolution of hepatic inflammation during Trypanosoma cruzi acute infection. These cells are identified in mice by the co-expression of the surface markers CD11b and Gr1 and there are two subsets: granulocytic (G-MDSCs:-CD11b+LY6G+LY6Clow) and monocytic (M-MDSCs:-CD11b+LY6G-LY6Chigh) phenotype. MDSCs suppress immune activation through several mechanisms such as reactive oxygen species (ROS) and nitric oxide (NO) production. Innate recognition through toll-like receptors (TLRs) on immune cells is critical not only for defense against T. cruzi but also for triggering hepatic pathology. Methods: We focus on analyzing the MDSCs phenotypes induced during acute T.cruzi infection in male C57BL/6 WT, TLR2-/- and TLR4-/- mice (1000 trypomastigotes i.p. injected-Tulahuen strain), parasitemia and transaminases in plasma as early tissue damage markers. Besides, ROS-producing M-and G-MDSCs were evaluated by flow cytometry. Results: The parasitemias at 19 dpi were higher in TLR2KO and TL4KO vs. WT mice. The total number of hepatic MDSCs was similar between mouse strains. However, a marked increase of M-MDSCs in infected TLR4KO vs. WT and TLR2KO mice (p<0,05) was observed. Conversely, the number of G-MDSCs remains low and was similar among mouse strains. Remarkably, in the liver of infected TLR4KO mice a higher number of ROS producing M-MDSCs was found. The infection produced a strong augment of ALT activity in TLR4KO while AST was increased in both KO mice.Conclusion: TLR4 would be important for the control of the severity during the acute T.cruzi infection through regulating M-MDSCs expansion within the liver.Keywords: Myeloid-derived suppressor cells, Trypanosoma cruzi, Toll like receptors, Reactive oxygen species