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

Area of Science:

• Immunology
• Microbiology
• Mycology

Background:

• Commensal intestinal microbes, like Candida albicans, play a key role in regulating systemic immunity.
• The impact of fungal heterogeneity on immunogenicity during host adaptation is not fully understood.

Purpose of the Study:

• To investigate the role of the transcriptional regulator UME6 in Candida albicans-primed systemic Th17 immunity.
• To determine how dynamic gene expression in C. albicans affects host immune responses.

Main Methods:

• Studied UME6 deletion and overexpression strains of C. albicans in mice.
• Analyzed the role of fungal cell wall components (β-glucan, mannan) in immune priming.
• Investigated host pattern recognition receptors (TLR2, TLR4, Dectin-1, Dectin-2) involved in Th17 immunity.

Main Results:

• UME6 is essential for intestinal C. albicans-primed systemic Th17 immunity.
• Oscillating UME6 expression, linked to β-glucan and mannan production, restored immunogenicity.
• Fungal cell wall components and C. albicans stimulate Th17 immunity via synergistic action of multiple host pattern recognition receptors.

Conclusions:

• Dynamic gene expression fluctuations in C. albicans are vital for priming host immunity against disseminated infections.
• UME6-mediated regulation of fungal morphology and cell wall composition is critical for immune priming during symbiotic colonization.