Open AccessRegulation of Innate Immune Response to Candida albicans Infections by α M β 2 -Pra1p Interaction
Author(s) -
Dmitry Aleksandrovich Soloviev,
Samir Jawhara,
William A. Fonzi
Publication year - 2011
Publication title -
infection and immunity
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.508
H-Index - 220
eISSN - 1070-6313
pISSN - 0019-9567
DOI - 10.1128/iai.00650-10
Subject(s) - candida albicans , biology , innate immune system , microbiology and biotechnology , corpus albicans , virulence , immune system , immunity , fungal protein , immunology , in vivo , yeast , gene , saccharomyces cerevisiae , biochemistry , genetics
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 toC. albicans is one of the main tasks of cells of the innate immune system, andin vitro evidence suggests that integrin αM β2 (CR3, Mac-1, and CD11b/CD18) is the principal leukocyte receptor involved in recognition of the fungus. Using αM β2 -KO mice and mutated strains ofC. albicans in two models of murine candidiasis, we demonstrate that neutrophils derived from mice deficient in αM β2 have a reduced ability to killC. albicans and that the deficient mice themselves exhibit increased susceptibility to fungal infection. Disruption of thePRA1 gene ofC. albicans , the primary ligand for αM β2 , protects the fungus against leukocyte killingin vitro andin vivo , impedes the innate immune response to the infection, and increases fungal virulence and organ invasionin vivo . Thus, recognition of pH-regulated antigen 1 protein (Pra1p) by αM β2 plays a pivotal role in determining fungal virulence and host response and protection againstC. albicans infection.