Innate immune receptors TLR9 and NLRP3 inflammasome might be involved in the inflammatory response and hepatic injury during Trypanosoma cruzi infection

PAROLI A; ONOFRIO L; AROCENA AR; CANO R

Mar del Plata

Congreso; LXII Reunión Anual de La Sociedad Argentina de Inmunología; 2014

Sociedad Argentina de Inmunología

Innate immune receptors TLR9 and NLRP3 inflammasome might be involved in the inflammatory response and hepatic injury during Trypanosoma cruzi infection Paroli, Augusto F.; Arocena, Alfredo; Onofrio, Luisina; Gea, Susana It has recently been reported a key role of the NLRP3 inflammasome in the defense against Trypanosoma cruzi Y strain infection. Cooperation between toll like receptors (TLRs) and NLRP3 has been proposed. We previously observed that the i.p. infection of C57BL/6 male mice with 1000 trypomastigotes-Tulahuén strain, increased the expression of nlrp3 and tlr9 mRNA in the liver, one of the infection?s target tissues, accompanied by a strong inflammatory response and increase of transaminases. We hypothesize that immune activation through TLR9 and inflammasome components might be involved in the hepatic damage during the acute phase. The aim of this work was to analyze the expression of TLR9 and NLRP3 in hepatic infiltrating macrophages and granulocytes, the presence of systemic, hepatic and intracellular IL-1β and the expression of IL-1 and IL-18 receptors on T lymphocytes during the acute phase of the infection in the proposed model vs. uninfected control group. Plasmatic levels of IL-1β showed a tendency to increase along the acute phase. IL-1β-p17 was only detectable in the hepatic tissue at 21 dpi by W. Blot. accompanied by increased number of F4/80+IL-1β+ and Gr1+IL-1β+ cells (*p<0,05; **p<0,01). At the same time, we found increased number of hepatic leukocytes expressing IL1R and IL18R. Hence, the number of CD4+IL1R+ and CD8+IL1R+ increased at 14 dpi (***p<0,001), and CD3+IL18R+ T lymphocytes were higher at both post infection times (***p<0,001). It was also observed a raise in both the number of F4/80+TLR9+ cells and in the MFI at 14 dpi (***p<001), with an increment of the F4/80+NLRP3+ cells at 21 dpi (*p<0,05). In addition, cells with the myeloid suppressor cell phenotype (Gr1+CD11b+) that expressed TLR9 or NLRP3 were augmented at 21 dpi (***p<0,001). Altogether, these results suggest a putative role of TLR9 and NLRP3 inflammasome in the exacerbated inflammatory response and the hepatic damage induced by the Tulahuén strain of T. cruzi.