Blockade of IL-33R/ST2 Signaling Attenuates Toxoplasma gondii Ileitis Depending on IL-22 Expression

Abstract

Oral <i>T. gondii</i> infection (30 cysts of 76K strain) induces acute lethal ileitis in sensitive C57BL/6 (B6) mice with increased expression of IL-33 and its receptor ST2 in the ileum. Here we show that IL-33 is involved in ileitis, since absence of IL-33R/ST2 attenuated neutrophilic inflammation and Th1 cytokines upon <i>T. gondii</i> infection with enhanced survival. Blockade of ST2 by neutralizing ST2 antibody in B6 mice conferred partial protection, while rmIL-33 aggravated ileitis. Since IL-22 expression further increased in absence of ST2, we blocked IL-22 by neutralizing antibody, which abrogated protection from acute ileitis in ST2 deficient mice. In conclusion, severe lethal ileitis induced by oral <i>T. gondii</i> infection is attenuated by blockade of ST2 signaling and may be mediated in part by endogenous IL-22.