MYCOLab Ai Logo - gold and army green

Abundant Yet Aberrant T Helper Cell Responses to Candida albicans Underlie Mucosal Candidiasis in Humans and Mice

Summary

Researchers studied how the immune system fights Candida albicans fungal infections. They found that a specific type of immune cell called Th17 cells is absolutely essential for controlling these infections, while other immune cells called Th2 cells actually make infections worse by blocking the protective Th17 cells. Patients with certain genetic mutations that affect how their immune system works have too many Th2 cells and not enough Th17 cells, making them vulnerable to chronic fungal infections. The study suggests that blocking a molecule called IL-4 could help restore the balance and improve patient outcomes.

Background

Candida albicans causes mucosal infections in immunocompromised individuals and those with chronic mucocutaneous candidiasis (CMC). T helper cell subsets, particularly Th17 cells, are known to coordinate pathogen-specific immune responses. Patients with STAT1 gain-of-function mutations display recurrent candidiasis despite preserved overall T cell responses.

Objective

To investigate whether altered T helper cell subset distribution in STAT1 gain-of-function patients with CMC contributes to disease susceptibility and to determine the relative contributions of Th1, Th2, and Th17 cells to protective immunity against mucosal Candida albicans infection.

Results

STAT1 gain-of-function patients exhibited numerically preserved but phenotypically skewed Candida-specific T cell responses dominated by Th1 and Th2 cells with reduced Th17 cells. In mouse models, only Th17 cells provided protective immunity against mucosal Candida infection, while Th2 cells were detrimental and suppressed Th17-mediated protection through IL-4 secretion. IL-4 neutralization restored Th17 expansion and protective immunity.

Conclusion

Th17 cells are essential and non-redundant for protective immunity against mucosal Candida albicans infection, while Th2 responses are ineffective and pathological. The skewed Th cell profile in STAT1 gain-of-function patients, characterized by elevated Th1/Th17 and Th2/Th17 ratios, contributes to chronic candidiasis. IL-4 neutralization represents a potential therapeutic strategy to restore protective immunity.
  • Published in:European Journal of Immunology,
  • Study Type:Clinical and Experimental Study,
  • Source: PMID: 41054009, DOI: 10.1002/eji.70065
Scroll to Top