Survival of Staphylococcus aureus inside neutrophils contributes to infection

Neutrophils have long been regarded as essential for host defense against S taphylococcus aureus infection. However, survival of the pathogen inside va rious cells, including phagocytes, has been proposed as a mechanism for per sistence of this microorganism in certain infections. Therefore, we investi gated whether survival of the pathogen inside polymorphonuclear neutrophils (PMN) contributes to the pathogenesis of S, aureus infection, Our data dem onstrate that PMN isolated from the site of infection contain viable intrac ellular organisms and that these infected PMN are sufficient to establish i nfection in a naive animal. In addition, we show that limiting, but not abl ating, PMN migration into the site of infection enhances host defense and t hat repletion of PMN, as well as promoting PMN influx by CXC chemokine admi nistration, leads to decreased survival of the mice and an increased bacter ial burden. Moreover, a global regulator mutant of S. aureus (sar-) that la cks the expression of several virulence factors is less able to survive and /or avoid clearance in the presence of PMN. These data suggest that the abi lity of S, aureus to exploit the inflammatory response of the host by survi ving inside PMN is a virulence mechanism for this pathogen and that modulat ion of the inflammatory response is sufficient to significantly alter morbi dity and mortality induced by S, aureus infection.