Staphylococcal superantigen-like 12 induces the production of interleukin 4 in murine basophils.

S. aureus is associated with atopic dermatitis (AD). Several staphylococcal products including cell wall components, protease, and exotoxins, are thought to be involved in allergic inflammation of AD via activating immune cells such as T cells and mast cells. None of the staphylococcal exotoxins has been reported to activate a primary IL-4 inducer, basophils, that are known to produce large amounts of IL-4 in response to allergens as well as IgE-independent stimuli such as mites and helminth proteases. In this study, we investigated the ability of staphylococcal superantigen-like (SSL) family to activate basophils. SSL12, reported its activity to activate mast cells, induced the production of IL-4 in bone marrow derived basophils. SSL12 also evoked the release of IL-4 in freshly isolated murine basophils in bone marrow cells, as the depletion of basophils by basophils-specific antibodies against high-affinity IgE receptor and CD49b diminished the responsiveness of bone marrow cells for SSL12. These results propose the novel immune regulatory activity of SSL12 by inducing IL-4 in basophils, that contributes to the development of allergic inflammation disorders and the immune evasion of the cocci.

Staphylococcal α-hemolysin does not induce cell damage in murine mast cells but it augments the degranulation induced by FcεRI cross-linking and ionomycin.

Staphylococcal α-hemolysin (Hla) is a principal small ß-barrel pore forming toxin. It targets a variety of mammalian cells including immune cells; however little is known about its effects on mast cells. In this study, we examined whether Hla affects the degranulation of mast cells. Although Hla bound to the surface of bone marrow-derived mast cells (BMMCs) and formed SDS-stable oligomers on the cells, Hla alone induced neither cytotoxicity nor obvious release of a granule enzyme, ß-hexosaminidase. However, Hla more than doubled the releases of ß-hexosaminidase from BMMCs induced by FcεRI cross-linking or treatment with ionomycin. The augmentation of the enzyme release by rHla was impaired in the presence of 130 mM of extracellular KCl. The mutants of Hla that lacked pore-formation did not augment the release of the enzyme. These findings demonstrate that Hla is able to enhance the degranulation of mast cells induced by FcεRI cross-linking and ionomycin, although it alone does not induce the degranulation, and the pore-formation of Hla followed by potassium efflux is involved in the augmentation. These findings propose a previously unrecognized role for Hla in S. aureus-associated allergic and inflammatory processes via augmentation of mast cell responses.