Adaptive immunity induces mutualism between commensal eukaryotes

Kyla S. Ost, Teresa R. O’Meara, W. Zac Stephens, Tyson Chiaro, Haoyang Zhou, Jourdan Penman, Rickesha Bell, Jason R. Catanzaro, Deguang Song, Shakti Singh, Daniel H. Call, Elizabeth Hwang-Wong, Kimberly E. Hanson, John F. Valentine, Kenneth A. Christensen, Ryan M. O’Connell, Brendan Cormack, Ashraf S. Ibrahim, Noah W. Palm, Suzanne M. Noble and June L. Round ()
Additional contact information
Kyla S. Ost: University of Utah School of Medicine
Teresa R. O’Meara: University of Michigan Medical School
W. Zac Stephens: University of Utah School of Medicine
Tyson Chiaro: University of Utah School of Medicine
Haoyang Zhou: University of Utah School of Medicine
Jourdan Penman: University of Utah School of Medicine
Rickesha Bell: University of Utah School of Medicine
Jason R. Catanzaro: Yale University School of Medicine
Deguang Song: Yale University School of Medicine
Shakti Singh: Harbor–UCLA Medical Center
Daniel H. Call: Brigham Young University
Elizabeth Hwang-Wong: Johns Hopkins University School of Medicine
Kimberly E. Hanson: University of Utah
John F. Valentine: University of Utah School of Medicine
Kenneth A. Christensen: Brigham Young University
Ryan M. O’Connell: University of Utah School of Medicine
Brendan Cormack: Johns Hopkins University School of Medicine
Ashraf S. Ibrahim: Harbor–UCLA Medical Center
Noah W. Palm: Yale University School of Medicine
Suzanne M. Noble: UCSF School of Medicine
June L. Round: University of Utah School of Medicine

Nature, 2021, vol. 596, issue 7870, 114-118

Abstract: Abstract 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 colonization1,2 and we show that immune selection against hyphae improves the competitive fitness of C. albicans. C. albicans exacerbates intestinal colitis3 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.

Date: 2021
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DOI: 10.1038/s41586-021-03722-w

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