Cell aggregation mediated by deletion in modulates fungal colonization and host immune responses in the skin.

is an emerging multi-drug-resistant fungal pathogen that colonizes the skin and causes invasive infections in hospitalized patients. Multi-cellular aggregative phenotype is widely reported in the isolates, but its role in skin colonization and host immune response is not yet known. In this study, we generated aggregative phenotype by deleting the gene in and determined the fungal colonization and host immune response using an intradermal mouse model of skin infection. Our results indicate that mice infected with Δ strain had significantly lower fungal load after 3 and 14 days post-infections compared to the non-aggregative wild-type and the reintegrated strain. The colonization of Δ is associated with increased recruitment of CD11b Ly6G neutrophils and decreased accumulation of CD11b Ly6 C inflammatory monocytes and CD11b MHCII CD64 macrophages. Furthermore, Th17 cells and type 3 innate lymphoid cells (ILCs) were significantly increased in the skin tissue of Δ infected mice. Our findings suggest that aggregative phenotype mediated by deletion in induces potent neutrophil and IL-17-mediated immune response and reduces fungal colonization in the skin.IMPORTANCE is a rapidly emerging fungal pathogen that can colonize hospitalized patients, especially in skin tissue, and cause invasive infections. isolates exhibit morphological heterogeneity, and the multicellular aggregative phenotype of is reported frequently in clinical settings. Understanding the role of fungal morphotypes in colonization, persistence, and immune response in the skin microenvironment will have potential applications in clinical diagnosis and novel preventive and therapeutic measures. Here, we utilized the murine model of intradermal infection and determined that the aggregative phenotype of as the result of gene deletion elicits potential innate and adaptive immune responses in mice. These observations will help explain the differences in the skin colonization and immune responses of the aggregative morphotype of and open the door to developing novel antifungal therapeutics.