Rac2 GTPase is essential for host defense against fungal infection

초록

The hemopoietic-specific Rho family GTPase Rac2 is essential for normal neutrophil functions. Mice deficient in Rac2 exhibited defects in neutrophil functions, including F-actin polymerization, adhesion, chemotaxis, and superoxide production. Neutrophils from a patient with a mutation (D57N) in Rac2 showed similar defects to those found in rac2-/- murine neutrophils. Rac2-null mice increased mortality in invasive Aspergillosis and human patient had multiple recurrent infections. In this study, we further investigated the role of Rac2 in host defense against fungal infection. Rac2-null mice were more susceptible to Aspergillus fumigatus infection than wild-type. Phagocytosis of serum-opsonized zymosan (SOZ) was normal in rac2-/- neutrophils, while FcgR-mediated phagocytosis was impaired. Superoxide production was also normal in response to SOZ, however FcgR-elicited NADPH oxidase activity was decreased in rac2-/- neutrophils. In addition, Rac2 selectively regulated neutrophil primary granule release in response to fMLP. Taken together, these observations suggest that Rac2 protects host from invading pathogens by regulating phagocytosis, superoxide production and degranulation.