Trypanosoma cruzi trans-sialidase initiates an ROR-γt–AHR-independent program leading to IL-17 production by activated B cells

We identified B cells as a major source for rapid, innate-like interleukin 17 (IL-17) production in vivo in response to Trypanosoma cruzi infection. IL-17(+) B cells exhibited a plasmablast phenotype, outnumbered T(H)17 cells and were required for optimal response to this pathogen. Using both murine and human primary B cells, we demonstrate that exposure to parasite-derived trans-sialidase in vitro was sufficient to trigger modification of the cell surface mucin, CD45, leading to Btk-dependent signaling and IL-17A or IL-17F production via an ROR-γt and AHR-independent transcriptional program. Our combined data suggest that generation of IL-17(+) B cells may be an unappreciated feature of innate immune responses required for pathogen control or IL-17-mediated autoimmunity.