title: Integrin αXβ₂ is a leukocyte receptor for Candida albicans and is essential for protection against fungal infections.
abstract: The opportunistic fungus Candida albicans is one of the leading causes of infections in immunocompromised patients, and innate immunity provides a principal mechanism for protection from the pathogen. In the present work, the role of integrin α(X)β₂ in the pathogenesis of fungal infection was assessed. Both purified α(X)β₂ and α(X)β₂-expressing human epithelial kidney 293 cells recognized and bound to the fungal hyphae of SC5314 strain of C. albicans but not to the yeast form or to hyphae of a strain deficient in the fungal mannoprotein, Pra1. The binding of the integrin to the fungus was inhibited by β-glucans but not by mannans, implicating a lectin-like activity in recognition but distinct in specificity from that of α(M)β₂. Mice deficient in α(X)β₂ were more prone to systemic infection with the LD₅₀ fungal inoculum decreasing 3-fold in α(X)β₂-deficient mice compared with wild-type mice. After challenging i.v. with 1.5 × 10⁴ cell/g, 60% of control C57BL/6 mice died within 14 d compared with 100% mortality of α(X)β₂-deficient mice within 9 d. Organs taken from α(X)β₂-deficient mice 16 h postinfection revealed a 10-fold increase in fungal invasion into the brain and a 2-fold increase into the liver. These data indicate that α(X)β₂ is important for protection against systemic C. albicans infections and macrophage subsets in the liver, Kupffer cells, and in the brain, microglial cells use α(X)β₂ to control fungal invasion.
authors: Department of Molecular Cardiology, Joseph J. Jacobs Center for Thrombosis and Vascular Biology, Cleveland Clinic, Cleveland, OH 44195, USA.
authors: Samir
authors: S
authors: Jawhara
authors: Elzbieta
authors: E
authors: Pluskota
authors: Dmitriy
authors: D
authors: Verbovetskiy
authors: Olena
authors: O
authors: Skomorovska-Prokvolit
authors: Edward F
authors: EF
authors: Plow
authors: Dmitry A
authors: DA
authors: Soloviev
mesh_terms: D000818:Animals; D002176:Candida albicans / Q000472:pathogenicity*; D002177:Candidiasis / Q000276:immunology* / Q000382:microbiology / Q000517:prevention & control*; D002448:Cell Adhesion / Q000276:immunology; D002460:Cell Line; D002465:Cell Movement / Q000276:immunology; D057899:Cytophagocytosis / Q000276:immunology; D057809:HEK293 Cells; D006801:Humans; D016167:Integrin alphaXbeta2 / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D007962:Leukocytes / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D011971:Receptors, Immunologic / Q000378:metabolism* / Q000502:physiology
chemical_list: D016167:Integrin alphaXbeta2; D011971:Receptors, Immunologic