Interaction of the fungal pathogen Candida albicans with integrin CD11b/CD18: recognition by the I domain is modulated by the lectin-like domain and the CD18 subunit.
Interactions of microorganisms with integrins are central to the host defense mechanisms. The leukocyte integrin CD11b/CD18 is the principal adhesion receptor on leukocytes for Candida albicans, a major opportunistic pathogen. In this study we have investigated the roles of three regions within the receptor, the inserted (I) and lectin-like domains within the CD11b subunit, and the CD18 subunit, in CD11b/CD18-C. albicans interactions. We report four major findings. 1) A mutation in CD18 exerts a dominant negative effect on the function of the CD11b/CD18 complex. This interpretation is based on the observation that in the absence of CD18, the CD11b subunit alone binds C. albicans well, but a single point mutation at Ser138 of CD18 abolishes CD11b/CD18 binding of the fungus. 2) The lectin-like domain is not sufficient for CD11b/CD18-C. albicans interactions. Rather, the lectin-like domain appears to influence CD11b/CD18 binding activity by modulating the function of the I domain. 3) The I domain is the primary binding site for C. albicans in the receptor and is sufficient to support an efficient interaction. 4) We have identified specific amino acid sequences within the I domain that engage the microorganism. Compared with other ligands of CD11b/CD18, C. albicans has some unique as well as common contact sites within the I domain of the receptor. Such unique contact sites may underlie the ability of C. albicans to modulate CD11b/CD18 function and raise the possibility for selective interference of the microorganism-host leukocyte interactions.
Forsyth
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CB
The Joseph J. Jacobs Center for Thrombosis and Vascular Biology, Department of Molecular Cardiology, The Cleveland Clinic Foundation, OH 44195, USA.
Plow
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Zhang
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D018821:CD18 Antigens / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D002176:Candida albicans / Q000276:immunology* / Q000472:pathogenicity; D002448:Cell Adhesion / Q000235:genetics / Q000276:immunology; D002460:Cell Line; D006801:Humans; D007376:Interleukin-2 / Q000494:pharmacology; D007668:Kidney; D037102:Lectins / Q000276:immunology / Q000378:metabolism* / Q000502:physiology; D008213:Lymphocyte Activation; D008214:Lymphocytes / Q000276:immunology / Q000382:microbiology; D016177:Macrophage-1 Antigen / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D008958:Models, Molecular; D010446:Peptide Fragments / Q000276:immunology / Q000378:metabolism* / Q000502:physiology; D010449:Peptide Mapping; D011485:Protein Binding / Q000276:immunology; D017434:Protein Structure, Tertiary; D014162:Transfection / Q000276:immunology
D018821:CD18 Antigens; D007376:Interleukin-2; D037102:Lectins; D016177:Macrophage-1 Antigen; D010446:Peptide Fragments