Staphylococcal Extracellular Complement‐Binding Protein Induces IL‐4 Production in Murine Basophils

ABSTRACT

Staphylococcus aureu s is responsible for a wide range of pyogenic infections, food poisoning, and allergic inflammation. S. aureus produces a very wide variety of proteinaceous exotoxins, which are classified by structure as β‐barrel pore‐forming toxin, oligonucleotide/oligosaccharide‐binding (OB)‐fold/β‐grasp proteins, and triple‐helix bundle‐containing proteins. We previously reported that three staphylococcal exotoxins belonging to the first two groups activate basophils and mast cells, which are innate immune cells that play a central role in allergic inflammation. In this study, we focused on a group of triple‐helix bundle‐containing toxins and examined their ability to activate murine bone marrow‐derived mast cells and basophils. Extracellular complement‐binding protein (Ecb), previously known as a complement inhibitor, was found to induce IL‐4 and IL‐6 production in basophils but not that of IL‐6 and IL‐13 in mast cells. Ecb did not induce IL‐4 production in murine splenocytes or CD4 ⁺ T cells, suggesting that it is a basophil‐specific activator. Ecb‐induced IL‐4 expression in basophils in the absence of serum. The C3‐binding‐deficient mutant of Ecb also activated basophils, indicating that Ecb activates basophils independently of its complement‐inhibiting activity. Dasatinib, a Src kinase inhibitor, prevented Ecb‐induced IL‐4 production in basophils, suggesting that the activation required a Src family kinase. These findings reveal a novel function of Ecb, that is, the activation of basophils to produce IL‐4 in an IgE‐independent manner, and suggest a dual Ecb contribution to immune evasion—by interfering with complement activation and skewing Th2 immunity—and a role in the development of allergic inflammation—by inducing IL‐4 production.