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Lymphocytes utilize CD11b/CD18 for adhesion to Candida albicans
1Department of Microbiology and Immunology, Stritch School of Medicine, University of Chicago, Maywood, Illinois 60153, USA.
Insights
Large granular lymphocytes use Mac-1 (CD11b/CD18) to adhere to Candida albicans hyphae, inhibiting fungal growth. This interaction is mediated by Mac-1 binding to microbial ligands and extracellular matrix proteins.
Area of Science:
- Immunology
- Microbiology
- Cell Biology
Background:
- Large granular lymphocytes (LGLs) play a role in fungal immunity.
- Adherence of LGLs to Candida albicans hyphae is crucial for inhibiting fungal growth.
Purpose of the Study:
- To identify the specific lymphocyte surface molecules responsible for adhesion to Candida albicans hyphae.
- To elucidate the molecular mechanisms underlying LGL-fungal interactions.
Main Methods:
- Utilized monoclonal antibodies targeting CD11b and CD18 subunits of Mac-1.
- Tested inhibition of lymphocyte adhesion using known Mac-1 protein ligands (vitronectin, laminin, fibrinogen) and RGD-containing peptides.
- Assessed the effect of carbohydrate N-acetyl-D-glucosamine on lymphocyte adhesion.
Main Results:
- Monoclonal antibodies against Mac-1 (CD11b/CD18) significantly inhibited LGL adhesion to C. albicans hyphae.
- Protein ligands of Mac-1, including extracellular matrix proteins and RGD peptides, also blocked this adhesion.
- N-acetyl-D-glucosamine, a known inhibitor of Mac-1-mediated yeast adhesion, similarly inhibited hyphal adhesion.
Conclusions:
- Mac-1 (CD11b/CD18) is the primary lymphocyte surface molecule mediating adhesion to Candida albicans hyphae.
- Microbial ligands and extracellular matrix proteins can activate lymphocyte Mac-1 for fungal adhesion.
- A model for Mac-1 activation by microbial ligands in LGL-fungal interactions is proposed.
Abstract:
Large granular lymphocytes require adherence to hyphae of Candida albicans to inhibit growth of this fungus. This study was undertaken to identify the lymphocyte surface structures that mediate this adhesion. Monoclonal antibodies specific for epitopes of the alpha subunit (CD11b) and the beta 2 subunit (CD18) of Mac-1 eliminated lymphocyte adhesion to C. albicans hyphae. Significant inhibition of lymphocyte adhesion to C. albicans was also achieved with known protein ligands of Mac-1. These proteins included the extracellular matrix proteins vitronectin, laminin, and fibrinogen as well as two engineered peptides containing RGD (arginine-glycine-aspartic acid) sequences. Carbohydrates including N-acetyl-D-glucosamine which have been demonstrated to inhibit Mac-l-mediated adhesion to whole yeast and yeast zymosan also blocked lymphocyte adhesion to hyphae. These results identify Mac-1 (CD11b/CD18) as the surface structure that mediates lymphocyte adhesion to C. albicans. A model is proposed for lymphocyte Mac-1 activation by microbial ligands.