التفاصيل البيبلوغرافية
| العنوان: |
Candida albicansoscillating UME6expression during intestinal colonization primes systemic Th17 protective immunity |
| المؤلفون: |
Shao, Tzu-Yu, Kakade, Pallavi, Witchley, Jessica N., Frazer, Corey, Murray, Kathryn L., Ene, Iuliana V., Haslam, David B., Hagan, Thomas, Noble, Suzanne M., Bennett, Richard J., Way, Sing Sing |
| المصدر: |
Cell Reports; May 2022, Vol. 39 Issue: 7 |
| مستخلص: |
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. UME6deletion and constitutive overexpression strains are non-immunogenic during commensal colonization, whereas immunogenicity is restored by C. albicansundergoing oscillating UME6expression 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. albicansstimulate 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. albicansduring symbiotic colonization are essential for priming host immunity against disseminated infection. |
| قاعدة البيانات: |
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