<b>Role of Effector T cells in Host Defense during Reinfection of C</b><b><i>andida auris</i></b>

<p dir="ltr"><i>Candida auris</i> is an emerging multidrug-resistant skin-tropic fungal pathogen that causes serious human infections. However, the factors that regulate <i>C. auris</i> skin infection <i>in vivo</i> are still unclear. In this study, we identified that, unlike <i>Candida albicans,</i> which induces IL-17-secreting protective effector Th17 cells, <i>C. auris</i> predominately induces IFNγ-secreting pathogenic Th1 cells during reinfection. Surprisingly, we found that IFNγ enhances skin infection of <i>C. auris</i> but not <i>C. albicans.</i> Mechanistically, IFNγ enhances skin infection of <i>C. auris</i> by dampening the protective IL-17 responses and increasing dermal damage. Furthermore, we identified that the development of Th1 cells occurs through IL-12, produced by <i>C. auris</i>-induced inflammatory macrophages and monocyte-derived dendritic cells. In addition, our findings reveal that <i>C. auris</i> unique cell wall outer mannan layer regulates the development of Th1 and Th17 cells. Collectively, our findings, for the first time, identified that <i>C. auris</i> induces IFNγ to persist in the skin. These findings help explain why <i>C. auris</i> but not <i>C. albicans</i> preferentially persist in the skin long-term, with the potential to identify novel therapeutic approaches to prevent and treat this emerging fungal pathogen in humans.</p>