Toxic Shock Syndrome Toxin 1 Induces Immune Response via the Activation of NLRP3 Inflammasome.

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

doi:10.3390/toxins13010068

Lianci Peng, Chao Ye + Show 8 more

Open Access

https://doi.org/10.3390/toxins13010068

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Abstract

Staphylococcus aureus is a Gram-positive opportunistic pathogen which causes infections in a variety of vertebrates. Virulence factors are the main pathogenesis of S. aureus as a pathogen, which induce the host’s innate and adaptive immune responses. Toxic shock syndrome toxin 1 (TSST-1) is one of the most important virulence factors of S. aureus. However, the role of nucleotide-binding oligomerization domain-like receptor family pyrin domain containing 3 (NLRP3) in TSST-1-induced innate immune response is still unclear. Here, purified recombinant TSST-1 (rTSST-1) was prepared and used to stimulate mouse peritoneal macrophages. The results showed that under the action of adenosine-triphosphate (ATP), rTSST-1 significantly induced interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) production in mouse macrophages and the production was dose-dependent. In addition, rTSST-1+ATP-stimulated cytokine production in macrophage depends on the activation of toll like receptor 4 (TLR4), but not TLR2 on the cells. Furthermore, the macrophages of NLRP3−/− mice stimulated with rTSST-1+ATP showed significantly low levels of IL-1β production compared to that of wild-type mice. These results demonstrated that TSST-1 can induce the expression of inflammatory cytokines in macrophages via the activation of the TLR4 and NLRP3 signaling pathways. Our study provides new information about the mechanism of the TSST-1-inducing host’s innate immune responses.

Highlights

Staphylococcus aureus (S. aureus) is a common Gram-positive extracellular pathogen causing severe infections, such as abscesses, osteomyelitis, septic arthritis, pneumonia and endocarditis [1]
Key Contribution: Our study reveals for the first time that inflammasome NLRP3 mediates the superantigen toxin Toxic shock syndrome toxin 1 (TSST-1)-induced inflammatory response, contributing to the development of therapeutics against S. aureus infection
Our study provides a better understanding on the interaction of TSST-1 and the host immunity, which contributes to the development of therapeutics against S. aureus infection

Summary

Introduction

Staphylococcus aureus (S. aureus) is a common Gram-positive extracellular pathogen causing severe infections, such as abscesses, osteomyelitis, septic arthritis, pneumonia and endocarditis [1]. During S. aureus infection, these virulence factors can induce innate immune responses and produce inflammatory or pro-inflammatory cytokines. Inflammasome family members contain NLRP1, NLRP3, NLRC4, NLRP6, NLRP7, NLRP12 and absent in melanoma 2 (AIM2) [16] These inflammasomes can be activated by different microbial stimuli to release inflammatory cytokines IL-1β and IL-18, which play an important role in the host’s innate immunity against microbial infection [17]. NLRC4 is assembled in response to the flagellin of Salmonella typhimurium and Legionella pneumophila, while AIM is the receptor of intracellular bacterial DNA such as Listeria monocytogenes [18,19,20] Among these inflammasomes, NLRP3 is one of the most extensively studied inflammasomes. Our study provides a better understanding on the interaction of TSST-1 and the host immunity, which contributes to the development of therapeutics against S. aureus infection

Expression and Purification of Recombinant TSST-1

Toxins

Statistical Analysis