Lymphocyte adhesion to Candida albicans.
Adherence of lymphocytes to the fungus is the first step in the direct lymphocyte-mediated antifungal effect against Candida albicans. In this study we identified macrophage-1 antigen (Mac-1) (CD11b/CD18, alpha(M)/beta(2)) as the lymphocyte surface structure responsible for the adhesion of activated lymphocytes to the hyphal form of the fungus. Antibodies specific for epitopes of the alpha-subunit (CD11b) and the beta(2)-subunit (CD18) of Mac-1 were shown to completely eliminate lymphocyte adhesion to C. albicans hyphae. Lymphocyte adhesion to C. albicans was also inhibited significantly by known ligands of Mac-1, including the extracellular matrix proteins laminin and fibrinogen, as well as engineered peptides containing arginine-glycine-aspartic acid sequences and the disintegrin echistatin. N-Acetyl-D-glucosamine and beta-glucan, which inhibit Mac-1-mediated adhesion to the yeast, blocked lymphocyte adhesion to hyphae. NIH 3T3 fibroblast transfectants expressing human CD11b/CD18 bound to C. albicans, and their binding was inhibited by antibodies specific for CD11b/CD18. Finally, antibodies specific for CD11b/CD18 effectively inhibited the capacity of activated lymphocytes to have an antifungal effect against hyphae. Our results clearly identify Mac-1 (CD11b/CD18) as the lymphocyte surface structure that mediates activated lymphocyte adhesion to C. albicans and the resultant antifungal effect of the lymphocytes.
Forsyth
Christopher B
CB
Department of Microbiology and Immunology, Loyola University of Chicago, Maywood, Illinois 60153, USA.
Mathews
Herbert L
HL
D016475:3T3 Cells; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D018821:CD18 Antigens / Q000235:genetics / Q000276:immunology*; D002176:Candida albicans / Q000276:immunology*; D002241:Carbohydrates / Q000494:pharmacology; D002448:Cell Adhesion / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D005260:Female; D005340:Fibrinogen / Q000494:pharmacology; D006801:Humans; D007797:Laminin / Q000494:pharmacology; D007963:Leukocytes, Mononuclear / Q000166:cytology; D008213:Lymphocyte Activation; D008214:Lymphocytes / Q000187:drug effects / Q000276:immunology*; D016177:Macrophage-1 Antigen / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009842:Oligopeptides / Q000494:pharmacology; D013154:Spleen / Q000166:cytology; D014162:Transfection
D000911:Antibodies, Monoclonal; D018821:CD18 Antigens; D002241:Carbohydrates; D007797:Laminin; D016177:Macrophage-1 Antigen; D009842:Oligopeptides; C047981:arginyl-glycyl-aspartic acid; D005340:Fibrinogen