摘要：SummaryBladder infection affects a hundred million people annually, but our understanding of bladder immunity is incomplete. We found type 17 immune response genes among the most up-regulated networks in mouse bladder following uropathogenicEscherichia coli(UPEC) challenge. Intravital imaging revealed submucosalRorc+ cells responsive to UPEC challenge, and we found increasedIl17andIL22transcripts in wild-type andRag2−/−mice, implicating group 3 innate lymphoid cells (ILC3s) as a source of these cytokines. NCR-positive and negative ILC3 subsets were identified in murine and human bladders, with local proliferation increasing IL17-producing ILC3s post infection. ILC3s made a more limited contribution to bladder IL22, with prominent early induction of IL22 evident in Th17 cells. Single-cell RNA sequencing revealed bladder NCR-negative ILC3s as the source of IL17 and identified putative ILC3-myeloid cell interactions, including via lymphotoxin-β-LTBR. Altogether, our data provide important insights into the orchestration and execution of type 17 immunity in bladder defense.Graphical abstractDisplay OmittedHighlights•Type 17 immune gene network is the major transcriptional response post bladder infection•Group 3 innate lymphoid cells (ILC3s) identified in mouse and human bladder•ILC depletion inRag2−/−mice resulted in increased bladder bacterial load•IL17 production by ILC3 shape bladder macrophage activation and polarizationImmunology; Cell biology; Transcriptomics
