Candida albicans is an opportunistic yeast pathogen and can cause life-threatening systemic candidiasis. The cell surface of C. albicans is enriched with mannan that is resistant to complement activation in the absence of antimannan antibodies. To better appreciate antimannan antibody functions in human immunity, our laboratory constructed the human recombinant antimannan Fc-free fragment M1 Fab. M1 Fab was subsequently converted to full-length human recombinant antimannan antibodies: M1g1 (IgG1), M1a1 (IgA1), M1a2 (IgA2). Each retains the identical M1 Fab binding region but differ in the isotype. Previously, our laboratory has established that M1 Fab can increase C3b deposition to C. albicans via the alternative pathway and that M1g1 activates the alternative and classical pathways of complement and increases phagocytosis of C. albicans by murine macrophages. The purpose of this study was to assess the influence of M1a1 and M1a2 on M1g1 mediated complement activation and phagocytosis of C. albicans. M1a1 or M1a2 was found unable to promote C3b-deposition to C. albicans as determined by flow cytometry and immunofluorescence microscopy. The formation of the alternative pathway convertase on C. albicans was promoted by M1 Fab but not by M1-Fab contained within M1a1 or M1a2. Additionally, M1g1 mediated C3b deposition was inhibited by M1a1 or M1a2 in a dose-dependent manner. Finally, M1a1 or M1a2 each significantly increased phagocytosis of C. albicans (P <0.001) by human neutrophils independent of serum. The presence of M1a1 or M1a2 did not inhibit M1g1-mediated phagocytosis, indicating a redundant function of IgG1 and IgA antibodies in opsonophagocytosis. Thus, human antimannan IgA subclass variants hinder complement activation while increasing neutrophil phagocytosis of C. albicans. These results contribute to a more complete understanding of the role of serum IgA in host immunity.
|Commitee:||Fraser, Deborah, Itatani, Carol|
|School:||California State University, Long Beach|
|School Location:||United States -- California|
|Source:||MAI 56/02M(E), Masters Abstracts International|
|Subjects:||Biology, Microbiology, Immunology|
|Keywords:||Antimannan, Candida albicans, Complement activation, IgA, IgG, Neutrophil phagocytosis|
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