Delta Hemolysin and Phenol-Soluble Modulins, but Not Alpha Hemolysin or Panton-Valentine Leukocidin, Induce Mast Cell Activation

Abstract

Mast cells are located at host interfaces, such as the skin, and contribute to the first-line defense against pathogens by releasing soluble mediators, including those that induce itching and scratching behavior. Here, we show that delta-hemolysin (Hld) and phenol soluble modulins (PSMs) PSMα1 and PSMα3, but not alpha-hemolysin (Hla) or Panton-Valentine leukocidin (PVL), induce dose-dependent tryptase, and lactate dehydrogenase (LDH) release by the HMC-1 human mast cell line. Using supernatants from isogenic strains, we verified that tryptase and LDH release was Hld- and PSMα-dependent. PSMα1 and Hld production was detected in 65 and 17% of human <i>Staphylococcus aureus</i>-infected skin abscess specimens, respectively, but they were produced <i>in vitro</i> by all clinical isolates. The results suggest that Hld and PSM-α1 produced <i>in vivo</i> during <i>S. aureus</i> skin infections induce the release of mast cell mediators responsible for itching and scratching behavior, which may enhance skin to skin transmission of <i>S. aureus via</i> the hands. As Hld and PSMs are upregulated by accessory gene regulator (agr), their association may contribute to the elective transmission of <i>S. aureus</i> strains with a functional agr system.