Nature. 2021 Aug;596(7870):114-118. doi: 10.1038/s41586-021-03722-w. | PubMed

Kyla S Ost^1,2, Teresa R O'Meara³, W Zac Stephens^1,2, Tyson Chiaro^1,2, Haoyang Zhou^1,2, Jourdan Penman^1,2, Rickesha Bell^1,2, Jason R Catanzaro⁴, Deguang Song⁵, Shakti Singh⁶, Daniel H Call⁷, Elizabeth Hwang-Wong⁸, Kimberly E Hanson⁹, John F Valentine¹⁰, Kenneth A Christensen⁷, Ryan M O'Connell^1,2, Brendan Cormack⁸, Ashraf S Ibrahim^6,11, Noah W Palm⁵, Suzanne M Noble¹², June L Round^13,14

1. Department of Pathology, Division of Microbiology and Immunology, University of Utah School of Medicine, Salt Lake City, UT, USA.
2. Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, USA.
3. Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, MI, USA.
4. Section of Pulmonology, Allergy, Immunology and Sleep Medicine, Department of Pediatrics, Yale University School of Medicine, New Haven, CT, USA.
5. Department of Immunobiology, Yale University School of Medicine, New Haven, CT, USA.
6. The Lundquist Institute of Biomedical Innovation, Harbor-UCLA Medical Center, Torrance, CA, USA.
7. Department of Chemistry and Biochemistry, Brigham Young University, Provo, UT, USA.
8. Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
9. Department of Pathology, Division of Clinical Microbiology, University of Utah, Salt Lake City, UT, USA.
10. Department of Internal Medicine, Division of Gastroenterology, University of Utah School of Medicine, Salt Lake City, UT, USA.
11. David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
12. Department of Microbiology and Immunology, UCSF School of Medicine, San Francisco, CA, USA.
13. Department of Pathology, Division of Microbiology and Immunology, University of Utah School of Medicine, Salt Lake City, UT, USA. june.round@path.utah.edu.
14. Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, USA. june.round@path.utah.edu.

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.

Presented By Kyla Ost | ORCID iD