Preferential binding of Staphylococcus aureus to skin sites of Th2-mediated inflammation in a murine model

Staphylococcus aureus is found on over 90% of atopic dermatitis skin lesion s and is thought to contribute to skin inflammation via the production of p otent exotoxins. In contrast, less than 5% of normal subjects harbor S. aur eus. This suggests that an atopic immune response itself may play a role in preferential binding of S. aureus to the skin. To examine this issue more directly, we analyzed the S, aureus binding characteristics of skin in mice undergoing different T helper type 1 cell versus T helper type 2 cell infl ammatory responses using a novel in vitro bacterial binding assay. BALB/C f emale mice were first sensitized to ovalbumin with alum or ovalbumin with c omplete Freund's adjuvant to induce T helper type 2 or T helper type 1 resp onses, respectively, Mice were then challenged intradermally with either sa line (control) or ovalbumin. Forty-eight hours later, skin specimens were o btained from the challenge sites, and the number of S. aureus binding to ea ch skin section was quantitated, Bacterial binding was found to be signific antly greater at skin sites of BALB/C mice that had been ovalbumin/alum sen sitized compared with ovalbumin/complete Freund's adjuvant sensitized (p le ss than or equal to 0.01). When compared to the ovalbumin sensitized/challe nged skin of wild type BALB/C mice or interferon-gamma gene knockout mice, interleukin-4, but not interferon-gamma, gene knockout mice had significant ly less S, aureus binding at their ovalbumin sensitized/challenged skin sit es, Mutant S, aureus strains that lacked either fibronectin- or fibrinogen- binding protein expression showed significantly reduced S, aureus binding c ompared with the parent wild type strain (p <0.005), Moreover, preincubatio n of the wild type bacteria with fibronectin or fibrinogen, but not collage n, resulted in significantly less skin binding of S. aureus (p < 0.01). Inc ubation of skin with interleukin-4, and less so with interferon-gamma, led to more binding of wild type S, aureus but not of an S. aureus mutant defic ient in fibronectin binding protein expression, After interleukin-4 incubat ion, but not interferon-gamma, epidermal immunoreactivity for fibronectin w as observed in murine skin explants. These results show that a T helper typ e 2 inflammatory environment can promote skin binding by S. aureus and that this binding is mediated by fibronectin and fibrinogen.