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Age-associated T cell dysfunction is a defining feature of inflammaging and immunosenescence, the progressive decline in immune competence observed with advancing age. Here we identified the association between aging (defined as age 60) and fungal dysbiosis, notably characterized by increased colonization of Candida species in the oral mucosa. There is also a notable enrichment of other taxa related to the order Saccharomycetales in older individuals. In contrast, younger individuals exhibit a greater abundance of Cryptococcus , Yarrowia , Kluyveromyces , and various Incertae sedis lineages. Further analysis, stratified by HIV status, shows that older individuals in both healthy and HIV+ groups display significantly higher levels of Candida. Gingival tissues reveal that both healthy older group and HIV-positive group exhibit elevated levels of CD4 + FOXP3 + regulatory T cells (T regs ) along with increased salivary concentrations of soluble TLR-2 and IL-6 compared to younger healthy group. Importantly, the abundance of Candida is positively correlated with elevated levels of mucosal T regs , dysfunctional T regs (T regDys ), and hyperactivated CD4 + T cells. In vitro experiments provided mechanistic insights by further demonstrating that Candida can induce both proliferation and dysfunction of T regs in an IL-6 dependent manner, supporting the notion that Candida plays a role in oral T cell senescence and inflammaging. Collectively, these findings underscore a direct relationship between the commensal mycobiome and T reg population, which normally promotes mucosal homeostasis but becomes susceptible to dysfunction with aging.
Jayaraman et al. (Thu,) studied this question.