期刊
NATURE
卷 596, 期 7870, 页码 114-+出版社
NATURE PORTFOLIO
DOI: 10.1038/s41586-021-03722-w
关键词
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资金
- Helen Hay Whitney Foundation
- University of Utah NRSA Microbial Pathogenesis T32 Training Grant
- CCFA Senior Research Award
- NIDDK [R01DK124336]
- NSF CAREER award [IOS-1253278]
- Packard Fellowship in Science and Engineering
- Burroughs Welcome Investigator in Pathogenesis Award
- American Asthma Foundation
- Margolis Foundation
- MS Society Center grant
- NIAID [R01046223, R01AI141202]
- NIH New Innovator Award [DP2GM111099-01]
- NHLBI [R00HL102228-05]
- American Cancer Society Research Grant
- Kimmel Scholar Award
- University of Utah Flow Cytometry Facility
- Center for High Performance Computing at the University of Utah
- Edward Mallinckrodt Jr. Foundation
- National Cancer Institute [5P30CA042014-24]
- [1 S10 OD018210 01A1]
- [R01AG047956]
The study reveals the crucial role of adaptive immune response in suppressing harmful fungal effectors, benefiting both Candida albicans and its host. IgA plays a key role in targeting specific adhesins to suppress the pathogenic hyphal morphotype of Candida, promoting intestinal homeostasis.
Pathogenic fungi reside in the intestinal microbiota but rarely cause disease. Little is known about the interactions between fungi and the immune system that promote commensalism. Here we investigate the role of adaptive immunity in promoting mutual interactions between fungi and host. We find that potentially pathogenic Candida species induce and are targeted by intestinal immunoglobulin A (IgA) responses. Focused studies on Candida albicans reveal that the pathogenic hyphal morphotype, which is specialized for adhesion and invasion, is preferentially targeted and suppressed by intestinal IgA responses. IgA from mice and humans directly targets hyphal-enriched cell-surface adhesins. Although typically required for pathogenesis, C. albicans hyphae are less fit for gut colonization(1,2) and we show that immune selection against hyphae improves the competitive fitness of C. albicans. C. albicans exacerbates intestinal colitis(3) and we demonstrate that hyphae and an IgA-targeted adhesin exacerbate intestinal damage. Finally, using a clinically relevant vaccine to induce an adhesin-specific immune response protects mice from C. albicans-associated damage during colitis. Together, our findings show that adaptive immunity suppresses harmful fungal effectors, with benefits to both C. albicans and its host. Thus, IgA uniquely uncouples colonization from pathogenesis in commensal fungi to promote homeostasis.
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