Resident Vδ1+ γδ T cells control early infiltration of neutrophils after Escherichia coli infection via IL-17 production

Neutrophils infiltrate the site of infection and play critical roles in host defense, especially against extracellular bacteria. In the present study, we found a rapid and transient production of IL-17 after i.p. infection with Escherichia coli, preceding the influx of neutrophils. Neutralization of IL-17 resulted in a reduced infiltration of neutrophils and an impaired bacterial clearance. Ex vivo intracellular cytokine flow cytometric analysis revealed that gamma delta T cell population was the major source of IL-17. Mice depleted of gamma delta T cells by mAb treatment or mice genetically lacking V delta 1 showed diminished IL-17 production and reduced neutrophil infiltration after E. coli infection, indicating an importance of V delta 1(+) gamma delta T cells as the source of IL-17. It was further revealed that gamma delta T cells in the peritoneal cavity of naive mice produced IL-17 in response to IL-23, which was induced rapidly after E. coli infection in a TLR4 signaling-dependent manner. Thus, although gamma delta T cells are generally regarded as a part of early induced immune responses, which bridge innate and adaptive immune responses, our study demonstrated a novel role of 75 T cells as a first line of host defense controlling neutrophil-mediated innate immune responses.