Project description:Under steady state conditions, the immune system is poised to sense and respond to the microbiota. As such, immunity to the microbiota, including T cell responses, is expected to precede any inflammatory trigger. How this pool of preformed microbiota-specific T cells contributes to tissue pathologies remains unclear. Here, using an experimental model of psoriasis, we show that recall responses to commensal skin fungi can significantly aggravate tissue inflammation. Enhanced pathology caused by fungi pre-exposure depends on Th17 responses and neutrophil extracellular traps and recapitulates features of the transcriptional landscape of human lesional psoriatic skin. Together, our results propose that recall responses directed to skin fungi can directly promote skin inflammation and that exploration of tissue inflammation should be assessed in the context of recall responses to the microbiota.
Project description:Diverse taxa of fungus kingdom are part of cancer related microbiota but which fungi induce pro-tumor immune responses and whether they impact specific cancer pathways are unclear. Here, we use Cladosporium cladosporioides to orally infect mice lacking Ikka in epithelial stem cells. This infection promotes systemic inflammation, acidic oral milieu with Proteobacteria expansion, and oral and skin squamous cell carcinoma (SCC) development. Double Stat3 and Ikka deletions reverse these phenotypes. We found in the serum of mouse, C. cladosporioides induces IL-17a and Il-1b production. To investigate what is happening in the oral environment as well as in the skin cells of mice, we conducted 10x genomics single cell RNA sequencing on mRNA in oral buccal tissues and skins from Ikka inducible ablated mouse with fungi treatment (Cladosporium cladosporioides).
