Regulation of innate immune response to Candida albicans infections by αMβ2-Pra1p interaction.
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)β₂ (CR3, Mac-1, and CD11b/CD18) is the principal leukocyte receptor involved in recognition of the fungus. Using α(M)β₂-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)β₂ 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)β₂, 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)β₂ plays a pivotal role in determining fungal virulence and host response and protection against C. albicans infection.
Joseph J. Jacobs Center for Thrombosis and Vascular Biology and Department of Molecular Cardiology, Cleveland Clinic, Cleveland, OH 44195, USA. solovjd@ccf.org
Dmitry A
DA
Soloviev
Samir
S
Jawhara
William A
WA
Fonzi
D000818:Animals; D002176:Candida albicans / Q000276:immunology* / Q000378:metabolism / Q000472:pathogenicity; D002177:Candidiasis / Q000276:immunology* / Q000378:metabolism; D002634:Chemotaxis, Leukocyte / Q000276:immunology; D005260:Female; D005455:Fluorescent Antibody Technique; D005656:Fungal Proteins / Q000276:immunology / Q000378:metabolism*; D007113:Immunity, Innate / Q000276:immunology*; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism; D016177:Macrophage-1 Antigen / Q000276:immunology / Q000378:metabolism*; D008297:Male; D008562:Membrane Glycoproteins / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009504:Neutrophils / Q000276:immunology / Q000378:metabolism; D014774:Virulence / Q000276:immunology; D037521:Virulence Factors / Q000276:immunology / Q000378:metabolism
D005656:Fungal Proteins; D016177:Macrophage-1 Antigen; D008562:Membrane Glycoproteins; C091515:PHR1 protein, Candida albicans; D037521:Virulence Factors
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