Caspase 1 activity impairs CD8+ T cells responses in coronavirus induced hepatitis.

DUHALDE VEGA M,; JELDRES, MATHIAS; HILL, MARCELO

Capri

Simposio; Advanced School of Immunology- T cell memory; 2018

Ceppellini School of Immunology

Activation of inflammasome triggers the cleavage of caspase-1 and maturation of IL1β, a critical step for an efficient infection control. The positive relation between IL1β release and adaptive immunity has been exhaustively described, but hepatitis seems to be negatively influenced by the inflammasome. In HCV patients, IL1β level is augmented and it has been associated with immunopathology and viral load. Therefore, the aim of this work was to analyze the role of the Caspase-1-IL1β axis in the initiation of adaptive immune responses. Inflammasome activation was analyzed on BMDCs derived from Casp1-/- and WT mice. Data have shown that MHV infection induced IL1β release on WT BMDCs, but not on Casp1-/-BMDCs. Then,in vivo studies have shown that Casp1-deficiency ameliorates MHV-induced hepatitis. Survival rates revealed that Casp1-/- mice are resistant to MHV infection, while only25% of WT mice survive at 20dpi. In accordance, liver from Casp1-/-mice showed reduced levels of MHV-RNA and augmented liver CD8-Tcells infiltration. Moreover, Casp1-/- mice have elevated number of MHV-specific CD8-T-cells and higher expression of CD107a marker. Finally, in vivo CTLactivity assay confirmed that Casp1-/-mice have higher MHV-specific CTL activity than WT mice. We found that Caspase1 activity is crucial in the modulation of CD8-T-cell response to coronavirus-induced hepatitis.