ATP Facilitates Staphylococcal Enterotoxin O Induced Neutrophil IL-1β Secretion via NLRP3 Inflammasome Dependent Pathways.

Fengqing Hou,Lianci Peng,Qingyuan Huang,Jiali Jiang,Tingting Chen,Dongyi Xu,Dong-Liang Hu,Rendong Fang,Chao Ye,Yuanyi Peng

doi:10.3389/fimmu.2021.649235

Fengqing Hou, Lianci Peng + Show 8 more

Open Access

https://doi.org/10.3389/fimmu.2021.649235

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Abstract

Staphylococcus aureus (S. aureus) is an important zoonotic food-borne pathogen causing severe invasive infections, such as sepsis, pneumonia, food poisoning, toxic shock syndrome and autoimmune diseases. Staphylococcal enterotoxin O (SEO) is a new type of enterotoxins of S. aureus with superantigenic and emetic activity. However, it is still unclear about SEO-induced host inflammatory response. Therefore, the mechanism of SEO-induced interleukin-1β (IL-1β) secretion in mouse neutrophils was investigated in this study. Our results showed that recombinant SEO had superantigenic activity with high level of gamma interferon (IFN-γ) production in mouse spleen cells and induced inflammatory cytokines expression including IL-1α, IL-1β, IL-6 and TNF-α in neutrophils under the action of ATP. In addition, SEO-induced IL-1β secretion was dependent on activation of Toll like receptor 4 (TLR4), nuclear factor kappa B (NF-κB) and c-jun N-terminal kinase (JNK) signaling pathways. However, SEO-induced IL-1β secretion was abolished in the neutrophils of NLRP3-/- mice compared with those of wild type mice, indicating that activation of NLRP3 inflammasome mediated IL-1β secretion during neutrophils stimulation with SEO under the action of ATP. Moreover, this process of SEO+ATP-induced IL-1β secretion was dependent on potassium (K+) efflux. Taken together, our study suggests that activation of TLR4/JNK/NLRP3 inflammasome signaling pathway mediate maturation and secretion of IL-1β and provides a new insight on S. aureus virulence factor-induced host immune response.

Highlights

Staphylococcal enterotoxins (SEs) are superantigenic exotoxins of S. aureus, in which are the leading causes of food poisoning [1]
The results demonstrated that activation of NLRP3 inflammasome and caspase-1 mediates maturation and secretion of IL-1b during neutrophils stimulation with Staphylococcal enterotoxin O (SEO) under the action of ATP and this process is dependent on K+ efflux
Another enterotoxin SEA and BSA were used as positive and negative control, respectively. Both of purified SEO and SEA stimulated spleen cells to produce IFN-g in a dose dependent manner compared with the BSA (Figure 1B). These results indicate that the recombinant SEO remains superantigenic activity

Summary

Introduction

Staphylococcal enterotoxins (SEs) are superantigenic exotoxins of S. aureus, in which are the leading causes of food poisoning [1]. Staphylococcal enterotoxin O (SEO) is a member of the new types of SEs with superantigenic and emetic activity [5, 6]. SEs can stimulate the massive proliferation of T cells by directly binding to major histocompatibility complex class II (MHC II) molecules of antigen presenting cells (APCs) and Vb regions of T cell receptor (TCR) [7,8,9], leading to the release of inflammatory cytokines including IL-2, TNF-a and IL-6 [1, 10]. It has been shown that SEA, SEB and SEC induced production of IL-1b and TNF-a in human alveolar macrophages and peripheral blood mononuclear cells [11, 12]. SEO-induced inflammatory response in the host is still unclear

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