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

In conclusion, severe lethal ileitis induced by oral T. gondii infection is attenuated by blockade of ST2 signaling and may be mediated in part by endogenous IL-22. Introduction Toxoplasma gondii is an opportunistic parasite with a worldwide distribution triggering an innate immune response. This response characterized by a rapid recruitment of neutrophils following the entry of infectious tachyzoites from the lumen into the intestinal mucosa eliciting a strong inflammatory Th1 response associated with the production of IFNγ, IL-12 and TNF-α. The parasite activates dendritic cells and macrophages to produce IL-12 leading to IFNγ expression (1). IL-17A is involved in neutrophil recruitment following infection, important for host defense and enhances a Th17 response via IL-17RA signaling (2). We found that IL-17RA deficient mice and B6 mice treated with neutralizing IL-17A antibody are more resistant to T. gondii induced acute ileitis as compared to infected B6 mice, suggesting that IL-17A contributes to the pathology of T. gondii inflammation (3). IL-33, previously known as IL1F11 or nuclear factor from high endothelial venules (4), is a member of the IL-1 cytokine family (1, 5). IL-33 in the nucleus is associated with chromatin, but the role of nuclear IL-33 is not yet clarified (6). Upon cell stress or death, biologically active IL-33 is released and truncated by proteolytic cleavage (7). IL-33 may have a dual role in different inflammatory c...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research