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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 Staphylococcus aureus-infected skin abscess specimens, respectively, but they were produced in vitro by all clinical isolates. The results suggest that Hld and PSM-α1 produced in vivo during S. aureus skin infections induce the release of mast cell mediators responsible for itching and scratching behavior, which may enhance skin to skin transmission of S. aureus via the hands. As Hld and PSMs are upregulated by accessory gene regulator (agr), their association may contribute to the elective transmission of S. aureus strains with a functional agr system.
Highlights
Microorganisms are increasingly being recognized to have profound effects on the host they invade (Shropshire and Bordenstein, 2016)
Because in vitro and in vivo studies in animals have been implicated PSMα1, PSMα3, Hld, Hla, and Panton-Valentine leukocidin (PVL) in the pathophysiology of skin infections, we examined their effect on HMC-1 cells by measuring the tryptase and lactate dehydrogenase (LDH) release
Using PSMα1, PSMα3, and Hld, tryptase levels correlated with the LDH levels, suggesting that tryptase release was directly linked to mast cell lysis (Supplementary Figure 3)
Summary
Microorganisms are increasingly being recognized to have profound effects on the host they invade (Shropshire and Bordenstein, 2016). In vitro and in vivo studies in animals have identified pore-forming toxins, such as Panton-Valentine leukocidin (PVL), alpha-hemolysin (Hla), phenol-soluble modulin-alpha (PSMα), and delta-hemolysin (Hld), as major virulence factors involved in the pathophysiology of staphylococcal skin infections (Wang et al, 2007; Kobayashi et al, 2011; Lipinska et al, 2011; Syed et al, 2015) These toxins are capable of targeting a wide variety of immune cells during infection, such as human polymorphonuclear leukocytes, monocytes, and macrophages, and can significantly contribute to dampening both innate and adaptive immune response to S. aureus infection (Pozzi et al, 2015)
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