Selective loss of gastrointestinal mast cells and impaired immunity in PI3K-deficient mice

Mice that lack the p85alpha regulatory subunit of phosphatidylinositol-3 kinase (PI3K) are deficient in gastrointestinal and peritoneal mast cells but have dermal mast cells. Accordingly, these mice show impaired bacterial clearance in response to acute septic peritonitis and are highly susceptible to infection by the intestinal nematode Strongyloides venezuelensis. Systemic anaphylactic shock responses, however, are intact. We found that although reconstitution of PI3K(-/-) mice with bone marrow-derived mast cells (BMMCs) restored anti-bacterial immunity, only T helper type 2 (T(H)2)-conditioned BMMCs, not standard BMMCs, were able to restore anti-nematode immunity. This finding highlights the importance of the T(H)2 response in the control of nematode infection. Thus, PI3K likely plays an essential role in host immune responses by regulating both the development and induction of mast cells.