Mucosal-associated Invariant T (MAIT) cells recognise antigens that derive from microbial riboflavin biosynthesis, presented on Major Histocompatibility Complex Class I-related 1 (MR1). Research using mouse models has revealed the therapeutic potential of MAIT cells in combating bacteria that utilize the riboflavin biosynthesis pathway. However, the interplay between MAIT cells and fungi that synthesise riboflavin remains poorly understood. Aspergillus fumigatus, an important opportunistic human pathogen, has been shown in studies in vitro to be recognized and responded to by human MAIT cells.
To dissect the involvement of MAIT cells during A. fumigatus infection, we employed several mouse models, including both immunocompetent and immunodeficient strains. Our findings present evidence that A. fumigatus induces activation and expansion of MAIT cells in various organs, including the lungs (following pulmonary infection), livers, spleens, and peripheral blood (following systemic infection) in immunocompetent C57BL/6 mice, while their role in immune protection is not readily observable. In contrast, in settings where other immune cells are deficient, such as CD4 T cell-deficient GK1.5 transgenic mice, MAIT cell-associated protection could be observed, as evidenced by better fungal control post systematic infection in comparison to MAIT-deficient GK1.5.MR1-/- mice. Moving forward, we will delve into the mechanisms underlying the protective role of MAIT cells in such conditions.
In summary, our findings underscore a potentially important, albeit partially redundant, role for MAIT cells in providing immune protection against A. fumigatus and suggest that the manipulation of MAIT cells holds promise as a potential therapeutic avenue for severely immunodeficient patients with invasive Aspergillus infection.