NLRP3 inflammasome and caspase-1/11 pathway orchestrate different outcomes in the host protection against trypanosoma cruzi acute infection
Date
2018Author
Paroli, Augusto Fabián
Díaz Luján, Cintia María
González, Patricia V.
Onofrio, Luisina Inés
Arocena, Alfredo Raúl
Cano, Roxana Carolina
Carrera Silva, Eugenio Antonio
Gea, Susana
Metadata
Show full item recordAbstract
Infection with protozoan parasite Trypanosoma cruzi results in activation of nucleotide-binding domain and leucine-rich repeat containing receptors (NLRs). NLR activation leads to inflammasome formation, the activation of caspase-1, and the subsequent cleavage of IL-1β and IL-18. Considering that inflammasome activation and IL-1β induction by macrophages are key players for an appropriate T cell response, we investigated the relevance of NLR pyrin domain-containing 3 (NLRP3) and caspase-1/11 to elucidate their roles in the induction of different T cell phenotypes and the relationship with parasite load and hepatic inflammation during T. cruzi-Tulahuen strain acute infection. We demonstrated that infected nlrp3-/- and C57BL/6 wild type (WT) mice exhibited similar parasitemia and survival, although the parasite load was higher in the livers of nlrp3-/- mice than in those of WT mice. Increased levels of transaminases and pro-inflammatory cytokines were found in the plasma of WT and nlrp3-/- mice indicating that NLRP3 is dispensable to control the parasitemia but it is required for a better clearance of parasites in the liver. Importantly, we have found that NLRP3 and caspase-1/11-deficient mice differentially modulate T helper (Th1, Th2, and Th17) and cytotoxic T lymphocyte phenotypes. Strikingly, caspase-1/11-/- mice showed the most dramatic reduction in the number of IFN-γ- and IL-17-producing CD4+ and CD8+ T cells associated with higher parasitemia and lower survival. Additionally, caspase-1/11-/- mice demonstrated significantly reduced liver inflammation with the lowest alanine aminotransferase (ALT) levels but the highest hepatic parasitic load. These results unequivocally demonstrate that caspase-1/11 pathway plays an important role in the induction of liver adaptive immunity against this parasite infection as well as in hepatic inflammation.
xmlui.dri2xhtml.METS-1.0.item-citation
Paroli, Augusto Fabián; Gonzalez, Patricia V.; Díaz Luján, Cintia María; Onofrio, Luisina Inés; Arocena, Alfredo Raul; et al.; NLRP3 Inflammasome and Caspase-1/11 Pathway Orchestrate Different Outcomes in the Host Protection Against Trypanosoma cruzi Acute Infection; Frontiers Media S.A.; Frontiers in Immunology; 9; 5-2018; 1-12
URI
https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2018.00913/fullhttp://hdl.handle.net/11086/550477