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© Research
Publication : Cell reports

Candida albicans oscillating UME6 expression during intestinal colonization primes systemic Th17 protective immunity.

Scientific Fields
Diseases
Organisms
Applications
Technique

Published in Cell reports - 17 May 2022

Shao TY, Kakade P, Witchley JN, Frazer C, Murray KL, Ene IV, Haslam DB, Hagan T, Noble SM, Bennett RJ, Way SS,

Link to Pubmed [PMID] – 35584674

Link to DOI – S2211-1247(22)00610-610.1016/j.celrep.2022.110837

Cell Rep 2022 05; 39(7): 110837

Systemic immunity is stringently regulated by commensal intestinal microbes, including the pathobiont Candida albicans. This fungus utilizes various transcriptional and morphological programs for host adaptation, but how this heterogeneity affects immunogenicity remains uncertain. We show that UME6, a transcriptional regulator of filamentation, is essential for intestinal C. albicans-primed systemic Th17 immunity. UME6 deletion and constitutive overexpression strains are non-immunogenic during commensal colonization, whereas immunogenicity is restored by C. albicans undergoing oscillating UME6 expression linked with β-glucan and mannan production. In turn, intestinal reconstitution with these fungal cell wall components restores protective Th17 immunity to mice colonized with UME6-locked variants. These fungal cell wall ligands and commensal C. albicans stimulate Th17 immunity through multiple host pattern recognition receptors, including Toll-like receptor 2 (TLR2), TLR4, Dectin-1, and Dectin-2, which work synergistically for colonization-induced protection. Thus, dynamic gene expression fluctuations by C. albicans during symbiotic colonization are essential for priming host immunity against disseminated infection.

https://pubmed.ncbi.nlm.nih.gov/35584674