Lack of Receptor for Advanced Glycation End Products Leads to Less Severe Staphylococcal Skin Infection but More Skin Abscesses and Prolonged Wound Healing

Background. Lack of receptor for advanced glycation end products (RAGE) ameliorates several infections including Staphylococcus aureus pneumonia. We sought to investigate the role of RAGE in staphylococcal skin infection in mice. Methods. Wild-type (WT) and RAGE deficient (RAGE(-/-)) mice were subcutaneously inoculated with S. aureus SH1000 strain in abscess-forming dose or necrotic dose. Clinical signs of dermatitis, along with histopathological changes, were compared between the groups. Results. The skin lesion size was smaller in RAGE(-/-) mice. Infected RAGE(-/-) mice expressed lower proinflammatory cytokines in local skins compared to control mice. Low dose of bacteria caused more abscess formation in RAGE(-/-) mice compared to skin necrosis that was more often observed in WT mice. As a result of more abscess formation, the wound healing was prolonged in RAGE(-/-) mice. Importantly, RAGE(-/-) mice had lower bacterial loads in the skin than controls, which is correlated with higher local levels of myeloperoxidase before skin infection. In vitro, enhanced phagocytic capacity of neutrophils and macrophages obtained from RAGE(-/-) mice compared to control mice was observed. Conclusions. RAGE deficiency up-regulates phagocytic capacity of phagocytes, resulting in lower bacterial burden in local skin and milder skin lesions in mice with staphylococcal skin infection.