Th17 Cells: Key to Candida Defense

T helper cell subsets—Th1, Th2, and Th17—coordinate pathogen-specific immune responses. Candida albicans-specific T cells include protective Th17 cells alongside other Th subsets. However, the role of alternative Th subsets remains unclear, particularly in individuals with impaired Th17 responses and recurrent candidiasis. Here, the authors show that patients with STAT1 gain-of-function mutations and chronic mucocutaneous candidiasis have a numerically normal but functionally altered pool of C. albicans-specific Th cells, skewed toward Th1 and Th2. This imbalance persisted even when assessing responses to the known and the newly identified immunodominant C. albicans antigens MP65 (65-kilodalton mannoprotein), HYR1 (hyphally regulated cell wall protein 1), and SAP4-6 (secreted aspartic proteinases 4–6), suggesting that antigen recognition and priming remain intact despite qualitative defects in T cell polarisation. Using mucosal infection mouse models, they demonstrate that C. albicans-specific transgenic Th17 cells are sufficient to control infection, whereas Th1 and Th2 cells fail to protect, even in high numbers. Moreover, co-transfer of Th2 cells with Th17 cells impaired fungal control via an IL-4-dependent mechanism. These findings highlight the essential role of Th17 cells in protective immunity against C. albicans and reveal that non-Th17 responses are ineffective and may contribute to susceptibility in both humans and mice.

Full article: https://onlinelibrary.wiley.com/doi/10.1002/eji.70065

WHY IS IT IMPORTANT?

Candida albicans is a fungus normally harmless in the mouth, gut, and skin, but it can cause chronic infections in patients with weakened immunity. This study shows that T helper cells, key immune cells, must be correctly balanced to fight Candida. Protective Th17 cells are essential, while other T cells (Th1 and Th2) are ineffective or even harmful. Patients with certain genetic mutations (STAT1-GOF) have normal numbers of Candida-specific T cells, but most are Th1 or Th2, reducing protection. Mouse experiments confirmed that only Th17 cells can clear mucosal infections, and Th2 cells can block their function. Understanding this imbalance is critical, as it could guide new treatments for chronic Candida infections and help prevent severe disease in vulnerable patients.

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