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Quantifying the Cytotoxicity of Staphylococcus aureus Against Human Polymorphonuclear Leukocytes
Published on: January 3, 2020
Staphylococcus sciuri exfoliative toxin C is a dimer that modulates macrophage functions
Haihua Li1, Xiaying Li, Ying Lu
1State Key Laboratory of Agrobiotechnology, College of Veterinary Medicine, China Agricultural University, Beijing 100193, People's Republic of China.
Abstract:
Staphylococcus sciuri causes multiple infections in humans. Recently, a strain of S. sciuri (HBXX06) carrying exfoliative toxin C (ExhC) was reported to cause fatal exudative epidermal skin pathology in piglets and might be considered as a potential zoonotic agent. However, little is known about the pathogenicity of this bacterium. In this study, we examined the activity of recombinant ExhC-his (rExhC) protein using newborn mice as the model and investigated the effect of rExhC on macrophage functions. Interestingly, we found that both rExhC and S. sciuri ExhC existed as dimers and that rExhC inhibited the phagocytosis of RAW264.7 cell lines but enhanced the production of proinflammatory mediators, such as interleukin-6, interleukin-12, tumor necrosis factor α, and nitric oxide, by murine peritoneal macrophages and RAW264.7 cells. These results suggest that ExhC may play an important role in innate immune response against S. sciuri infection.
Insights
Staphylococcus sciuri exfoliative toxin C (ExhC) inhibits macrophage phagocytosis and enhances inflammatory mediator production. This suggests ExhC plays a key role in the innate immune response to S. sciuri infections.
Area of Science:
- Microbiology
- Immunology
- Toxicology
Background:
- Staphylococcus sciuri is a pathogen causing human infections.
- A strain of S. sciuri carrying exfoliative toxin C (ExhC) has been linked to severe skin pathology in piglets and potential zoonotic transmission.
- The pathogenicity of S. sciuri, particularly the role of ExhC, remains poorly understood.
Purpose of the Study:
- To investigate the pathogenicity of Staphylococcus sciuri exfoliative toxin C (ExhC).
- To examine the effects of recombinant ExhC (rExhC) on macrophage functions in vitro and in vivo.
- To elucidate the role of ExhC in the innate immune response to S. sciuri.
Main Methods:
- Production and purification of recombinant ExhC protein with a histidine tag (rExhC-his).
- Assessment of rExhC activity using newborn mice as a model.
- Investigation of rExhC's impact on macrophage phagocytosis using RAW264.7 cell lines.
- Measurement of proinflammatory mediator production (interleukin-6, interleukin-12, tumor necrosis factor α, nitric oxide) by murine peritoneal macrophages and RAW264.7 cells upon exposure to rExhC.
Main Results:
- Both native S. sciuri ExhC and rExhC were found to exist as dimers.
- rExhC significantly inhibited the phagocytic activity of RAW264.7 cells.
- rExhC enhanced the production of key proinflammatory mediators, including IL-6, IL-12, TNF-α, and nitric oxide, in macrophages.
Conclusions:
- Exfoliative toxin C (ExhC) from Staphylococcus sciuri exhibits immunomodulatory functions.
- ExhC's ability to inhibit phagocytosis and stimulate inflammatory responses suggests a significant role in the pathogenesis of S. sciuri infections.
- ExhC may be a crucial factor in how S. sciuri evades or manipulates the host innate immune system.
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