Paradoxical role for the lipid phosphatase SHIP1 in control of helminth infection (147.29)

Abstract

Abstract Immunity to helminth infections is mediated by polarized Th2 responses that lead to clearance of infection. One of these responses is the development of AAMs that are associated with intestinal repair and parasite killing. SHIP1 is a lipid phosphatase that negatively regulates immune receptor signaling. Ship1-deficiency in macrophages results in a skewing towards a Th2-type response and the spontaneous development of AAMs. Thus, we hypothesized that macrophage-specific Ship1 knockout mice (Ship1ΔMac) mice would display increased resistance to Trichuris infection. Following infection with Trichuris, cells isolated from Ship1ΔMac mice produced equivalent levels of IL-4, IL-13 and IFN-γ compared to control Ship1fl/fl mice, suggesting that lack of Ship1 in macrophages had little effect on the development of Th2 responses in vivo. Strikingly however-and in contrast to our expectations-Ship1ΔMac mice were more susceptible to infection with Trichuris than control Ship1fl/fl mice. These results demonstrate that macrophage-specific expression of Ship1 is critical for resistance to Trichuris independently of a normally protective Th2 cell response and suggest an alternative role for AAMacs in helminth infection. Thus, these studies identify a novel and paradoxical role for Ship1 in the development of immunity to Trichuris and suggest that manipulation of macrophage function could be critical for inducing or limiting immune responses in the intestine.