A c-type lectin triggers immune surveillance by innate lymphoid cells for eradication of attaching-and-effacing bacteria.

Although gut protection to infection is ensured by innate lymphoid cells (ILCs), how ILCs are regulated remains poorly understood. Here, we show that secretion of the c-type lectin Reg3b downstream of Ripk2 signaling pathway was crucial for immune surveillance by ILCs against Citrobacter rodentium that mimics human infection with attaching-and-effacing bacteria. Unexpectedly, phosphorylation of signal transducer and activator of transcription 3 (STAT3) and secretion of both tumor necrosis factor alpha (Tnf-a) and interleukin-17A (IL-17A) were blunted in mutant mice contributing to their susceptibility to a primary infection. We further determined that influx of neutrophils was triggered by Reg3b through an intact IL-17A signaling. Loss of either Reg3b or Ripk2 weakened Tnf-a secretion by intestinal phagocytes lowering their propensity to promote IL17A secretion by ILCs early in infection. These results provide a previously unrecognized mechanism by which intestinal epithelial cells reciprocally regulate early production of IL-17A by ILCs preventing from overcolonization by opportunistic enteropathogenic bacterium. Microarray analysis was performed by using total tissue from caecum tip of mice on days 0, 4 and 12 post-infection (n = 5). Changes (log2-fold) in gene expression profiles of Ripk2-/-, Nod2-/- and WT mice on day 4 p.i. and on day 12 p.i. were calculated relative to non-infected WT controls and compared by correlation analysis.