T‐cell regulation of neutrophil trafficking during Staphylococcus aureus infections can regulate pathogenesis outcomes

Neutrophils are the first line of host‐defense in S. aureus infection and are critical in determining disease outcome. Evidence also suggests that S. aureus can survive inside neutrophils to exacerbate infection. We now demonstrate CXC chemokine‐induced internalization of S. aureus by neutrophils at the infection site using a murine model of surgical wound infection. To elucidate mechanisms controlling neutrophil recruitment to the infection site, we explore the novel concept that a sub set of neutrophil regulating T‐cells are activated during S. aureus infection and control the local neutrophil response. We demonstrate that S. aureus ‐capsular polysaccharide ‐8 can activate T‐cell production of Interferon‐γ (IFN‐γ) in a MHC‐class II pathway dependant manner. We observe increased production of IFN‐γ locally during S. aureus wound infection, a process dependent upon αβTCR+ T‐cells. In addition IFN‐γ−/− mice demonstrate decreased CXC chemokine production and associated neutrophil recruitment to the infection site compared to wild‐type mice. This reduced neutrophil influx is associated with lower tissue bacterial burden, suggesting that a neutrophil rich environment potentiates pathogenesis due to the bacteria's ability to survive within the neutrophil. It is clear that neutrophil recruitment must be tightly controlled during wound infection and we identify IFN‐γ as a central regulator of this process.