Identification of pH-Regulated Antigen 1 Released from Candida albicans as the Major Ligand for Leukocyte Integrin αMβ2

• Published in: The Journal of immunology (1950) 2007-02, Vol.178 (4), p.2038-2046
• Main Authors: Soloviev, Dmitry A., Fonzi, William A., Sentandreu, Rafael, Pluskota, Elzbieta, Forsyth, Christopher B., Yadav, Satya, Plow, Edward F.
• Format: Article
• Language: English
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.178.4.2038

Candida albicans is a common opportunistic fungal pathogen and is the leading cause of invasive fungal disease in immunocompromised individuals. The induction of cell-mediated immunity to C. albicans is of critical importance in host defense and the prime task of cells of the innate immune system. We previously demonstrated that the integrin αMβ2 (CD11b/CD18) is the major leukocyte receptor involved in C. albicans recognition, mediating both adhesive and migratory responses to the fungus. In the present study, we demonstrate that various C. albicans strains release a protease-sensitive activity into their conditioned medium that supports αMβ2-mediated cell adhesion and migration. The isolation and characterization of this protein was undertaken by two independent approaches: 1) immunoaffinity purification on a mAb raised to conditioned medium which blocked αMβ2-dependent adhesion and migration; and 2) affinity chromatography on purified αMβ2. Each approach led to the isolation of the same protein, which was unequivocally identified as pH-regulated Ag 1 (Pra1p), based on mass spectrometry and amino acid sequence analyses. C. albicans mutant strains lacking Pra1p were unable to support leukocyte adhesion or migration. In a neutrophil-mediated fungal killing assay, such mutant strains were resistant to killing and/or phagocytosis. Addition of purified Pra1p or reagents that block αMβ2 function prevented killing of Pra1p-expressing but not Pra1p-deficient strains of C. albicans. Together, these data indicate that Pra1p is a ligand of αMβ2 on C. albicans and that the soluble form of Pra1p may assist the fungus in escaping host surveillance.