Extracellular attaching and effacing (A/E) pathogens including pathogenic
Escherichia colicolonize the host gut causing diarrhea and inflammation. Although much is known regarding the pathogenesis of A/E bacteria, there remains an incomplete understanding of host immune responses to these microbes. NK cells are an important source of IFN‐γ and are essential for early innate responses to viral pathogens; however, their role during extracellular bacterial infections is still largely unexplored. We studied the host response to the murine A/E pathogen Citrobacter rodentiumto investigate NK‐cell function during infection. NK1.1+ cell depletions and analysis of colonic intestinal inflammation following Citrobacterinfection demonstrated that CD3−NK1.1+ cells play an important role in the initial clearance of C. rodentium, as evidenced by higher bacterial load, intestinal pathology, and crypt hyperplasia at the peak of inflammation in depleted mice. Loss of CD3−NK1.1+ cells resulted in lower colonic IFN‐γ, TNF‐α, and IL‐12, and a delay in homing of IFN‐γ+CD4+ T cells to the gut. Loss of this response resulted in lower anti‐ C. rodentiumIgG in NK1.1‐depleted mice. These data establish that CD3−NK1.1+ cells are critical for inducing an early Th1 response involved in clearance of a pathogen that is restricted to the gastrointestinal tract.