Role of Neutrophil Leukocytes in Cutaneous Infection Caused byStaphylococcus aureus

Abstract

Despite the high prevalence of cutaneous infections, little is known about the role of host immune responsiveness during Staphylococcus aureus dermatitis. We have recently described a murine model of infectious dermatitis induced by superantigen-producing S. aureus. To assess the role of neutrophils in staphylococcal dermatitis, mice were given granulocyte-depleting monoclonal antibody prior to and on several occasions following intracutaneous inoculation with staphylococci. The granulocyte-depleted mice that had been intradermally inoculated with S. aureus developed crusted ulcerations which tended not to heal, whereas animals injected with control monoclonal antibody displayed only minor and transient skin lesions. The finding of severe ulcerations in neutropenic mice correlated with a significantly higher burden of bacteria in the blood and skin during the early phase of the infection. Importantly, while mice with an intact granulocyte population showed only limited skin infection, bacteremia occurred in the great majority of the neutrophil-depleted animals. As a consequence, the latter individuals exhibited significantly increased levels of the proinflammatory cytokine interleukin-6 and specific antibodies to staphylococcal cell wall components and toxic shock syndrome toxin-1 in the serum. Our data point to a crucial protective role of granulocytes in S. aureus dermatitis.Neutrophils are host immune defense cells that are among the first to migrate into the skin in response to invading pathogens. These cells respond to chemotactic signals present at the site of infection. Among the roles played by neutrophils in inflammatory and immune responses are phagocytosis and killing of bacteria via the generation of reactive oxygen intermediates and the release of lytic enzymes stored in granules. In a recently described model of infectious dermatitis induced by the toxic shock syndrome toxin-1 (TSST-1)-producing Staphylococcus aureus strain LS-1 (12), healthy mice inoculated with high doses of staphylococci (10 8 CFU) displayed clinical and histopathological signs of local infection and inflammation within 48 h but lacked clinical or bacteriological signs of sepsis. The aim of this study was to evaluate the role of neutrophils in the induction, progression, and outcome of infectious dermatitis induced by intradermal injection of TSST-1-producing S. aureus. Our results show that depletion of neutrophil granulocytes both increases the severity of the skin lesion and gives rise to generalized infection, including bacteremia. These data demonstrate a crucial protective role for neutrophil granulocytes in S. aureus dermatitis. MATERIALS AND METHODSMice. Male BALB/c mice, 5 to 6 weeks old, were purchased from B&K Universal AB (Sollentuna, Sweden). They were housed in the animal facility of the Department of Rheumatology, University of Göteborg, under standard conditions of light and temperature and fed standard laboratory chow and water ad libitum.Bacterial strain. The BALB/c mice were inoculated intracutaneously with S....

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