Regulation of Innate Immune Response to Candida albicans Infections by α M β 2 -Pra1p Interaction

Abstract

ABSTRACT Candida albicans is a common opportunistic fungal pathogen and is the leading cause of invasive fungal diseases in immunocompromised individuals. The induction of cell-mediated immunity to C. albicans is one of the main tasks of cells of the innate immune system, and in vitro evidence suggests that integrin α M β 2 (CR3, Mac-1, and CD11b/CD18) is the principal leukocyte receptor involved in recognition of the fungus. Using α M β 2 -KO mice and mutated strains of C. albicans in two models of murine candidiasis, we demonstrate that neutrophils derived from mice deficient in α M β 2 have a reduced ability to kill C. albicans and that the deficient mice themselves exhibit increased susceptibility to fungal infection. Disruption of the PRA1 gene of C. albicans , the primary ligand for α M β 2 , protects the fungus against leukocyte killing in vitro and in vivo , impedes the innate immune response to the infection, and increases fungal virulence and organ invasion in vivo . Thus, recognition of pH-regulated antigen 1 protein (Pra1p) by α M β 2 plays a pivotal role in determining fungal virulence and host response and protection against C. albicans infection.