Advances in medicine have led to improved treatments including transplantation for end-stage organ disease, chemotherapy for cancer, and immunomodulatory and immunosuppressive therapies for autoimmune diseases. While these approaches have revolutionized treatment for these diseases, these therapies portend an increased susceptibility to infections, including those due to invasive fungi. Although Candida albicans is a widespread commensal in the human gut and skin, it is the primary Candida spp. that causes invasive candidiasis. Indeed, Candida spp. is the most common cause of hospital-acquired bloodstream fungal infections and fifth among all pathogens. Human SNPs in the type I interferon (IFN) pathway have been associated with increased susceptibility to candidemia. While these data suggest a significant role of type I IFNs in C. albicans host defense, the signaling pathway that licenses type I IFN production and regulation during C. albicans infection remains elusive.

Although small in numbers, plasmacytoid dendritic cells (pDCs) are the primary producers of type I IFNs (IFNα and IFNβ) in response to viral and bacterial pathogens though other cells (i.e., macrophages and monocytes) contribute to type I IFN production as well. Although induction of type I IFNs are well described in response to viral and bacterial pathogens, a crucial knowledge gap remains with respect to the mechanisms by which this pathway affects fungal pathogenesis. Using genetic models, we observed that the absence of critical IFN signaling components mice resulted in striking resistance to candidemia, but at the cost of a higher fungal burden. Furthermore, addition of type I IFNs improved killing capacity of neutrophils in response to C. albicans. These exciting data suggest that dysregulation of IFN signaling significantly affects the outcomes of invasive Candida infections. Thus, our long-term goal is to understand the regulation and role of type I IFNs in host defense against invasive candidiasis. This work will provide greater understanding of type I IFN response to invasive candidiasis and may lead to novel therapeutic targets to modulate the immune response to alter clinical outcomes in patients with candidiasis.

Z-stacked video of Candida biofilm