Journal
MOLECULAR IMMUNOLOGY
Volume 48, Issue 15-16, Pages 2009-2018Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.molimm.2011.06.215
Keywords
Cryptococcus; Complement
Categories
Funding
- Ford Foundation
- NIH [R01 AI51415, R01 AI071025, CA-16042, AI-28697]
- Veterans Affairs Merit Award
- Jonsson Cancer Center
- UCLA AIDS Institute
- UCLA School of Medicine
- UCLA MIMG Department
- UCLA Muscular Dystrophy Translational Research Consortium
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Complement can be activated via three pathways: classical, alternative, and lectin. Cryptococcus gattii and Cryptococcus neoformans are closely related fungal pathogens possessing a polysaccharide capsule composed mainly of glucuronoxylomannan (GXM), which serves as a site for complement activation and deposition of complement components. We determined 0 deposition on Cryptococcus spp. by flow cytometry and confocal microscopy after incubation with serum from C57BL/6J mice as well as mice deficient in complement components C4, C3, factor B, and mannose binding lectin (MBL). C. gattii and C. neoformans activate complement in EGTA-treated serum indicating that they can activate the alternative pathway. However, complement activation was seen with factor B-/- serum suggesting activation could also take place in the absence of a functional alternative pathway. Furthermore, we uncovered a role for C4 in the alternative pathway activation by Cryptococcus spp. We also identified an unexpected and complex role for MBL in complement activation by Cryptococcus spp. No complement activation occurred in the absence of MBL-A and -C proteins although activation took place when the lectin binding activity of MBL was disrupted by calcium chelation. In addition, alternative pathway activation by C. neoformans required both MBL-A and -C, while either MBL-A or -C was sufficient for alternative pathway activation by C. gattii. Thus, complement activation by Cryptococcus spp. can take place through multiple pathways and complement activation via the alternative pathway requires the presence of C4 and MBL proteins. Published by Elsevier Ltd.
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