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Publication : Integrin αXβ₂ is a leukocyte receptor for Candida albicans and is essential for protection against fungal infections.

First Author  Jawhara S Year  2012
Journal  J Immunol Volume  189
Issue  5 Pages  2468-77
PubMed ID  22844116 Mgi Jnum  J:189864
Mgi Id  MGI:5447138 Doi  10.4049/jimmunol.1200524
Citation  Jawhara S, et al. (2012) Integrin alphaXbeta(2) is a leukocyte receptor for Candida albicans and is essential for protection against fungal infections. J Immunol 189(5):2468-77
abstractText  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 alpha(X)beta(2) in the pathogenesis of fungal infection was assessed. Both purified alpha(X)beta(2) and alpha(X)beta(2)-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 beta-glucans but not by mannans, implicating a lectin-like activity in recognition but distinct in specificity from that of alpha(M)beta(2). Mice deficient in alpha(X)beta(2) were more prone to systemic infection with the LD(5)(0) fungal inoculum decreasing 3-fold in alpha(X)beta(2)-deficient mice compared with wild-type mice. After challenging i.v. with 1.5 x 10(4) cell/g, 60% of control C57BL/6 mice died within 14 d compared with 100% mortality of alpha(X)beta(2)-deficient mice within 9 d. Organs taken from alpha(X)beta(2)-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 alpha(X)beta(2) is important for protection against systemic C. albicans infections and macrophage subsets in the liver, Kupffer cells, and in the brain, microglial cells use alpha(X)beta(2) to control fungal invasion.
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