TLR2, TLR4, and NLRP3 mediated the balance between host immune-driven resistance and tolerance in Staphylococcus aureus-infected mice.

Abstract

Staphylococcus aureus (S. aureus) is a gram-positive pathogen that can cause infectious diseases in mammals. S. aureus-induced host innate immune responses have a relationship with Toll-like receptor 2 (TLR2), TLR4, and Nod-like receptor pyrin domain-containing protein 3 (NLRP3). However, the detailed roles of TLR2, TLR4, and NLRP3 in regulating the host inflammatory response to S. aureus infection remain unclear. Our data indicated that the S. aureus-induced mortality was aggravated by deficiency of TLR2, TLR4, and NLRP3 in mice. In the subsequent experiment, we found that during S. aureus infection, the roles of TLR2, TLR4, and NLRP3 seemed to be different at multiple timepoints. The deficiency of TLR2, TLR4, or NLRP3 attenuated the expression of High-mobility group box protein 1 (HMGB1) and Hyaluronic acid-binding protein 2 (HABP2), which is accompanied by decreased proinflammatory cytokine (TNF-α), chemokine (RANTES), and anti-inflammatory cytokine (IL-10) production in lungs and serum at 3 h and 6 h post-infection. However, with S. aureus infection prolonged (24 h post-infection), the trend was diametrically opposite. The results showed that deficiency of TLR2, TLR4, or NLRP3 aggravated HABP2 and HMGB1 expression, which is accompanied by enhanced proinflammatory cytokine (TNF-α), chemokine (RANTES), and anti-inflammatory cytokine (IL-10) production in lungs and serum. These results were consistent with the data observed in S. aureus-infected bone marrow-derived macrophages (BMDMs). All these results suggested that during S. aureus infection, TLR2, TLR4, and NLRP3 has time-dependent effect in regulating the balance between immune-driven resistance and tolerance.

• Authors: Zhiguo Gong, Jing Zhang, Shuangyi Zhang, Jinshan Cao, Yunhe Fu, Xiaoyu Hu, Jiamin Zhao, Baichen Gu, Qianru Li, Kai Zhang, Peipei Ren, Bo Liu, Wei Mao
• Journal: Microbial pathogenesis (Microb Pathog) Vol. 169 Pg. 105671 (Aug 2022) ISSN: 1096-1208 [Electronic] England
• PMID: 35811022 (Publication Type: Journal Article)
• Copyright: Copyright © 2022 Elsevier Ltd. All rights reserved.

Chemical References

• Chemokine CCL5
• Cytokines
• HMGB1 Protein
• NLR Family, Pyrin Domain-Containing 3 Protein
• Nlrp3 protein, mouse
• Tlr2 protein, mouse
• Tlr4 protein, mouse
• Toll-Like Receptor 2
• Toll-Like Receptor 4
• Tumor Necrosis Factor-alpha
• Interleukin-10

Topics

• Animals
• Chemokine CCL5
• Cytokines
• HMGB1 Protein
• Interleukin-10
• Mammals (metabolism)
• Mice
• Mice, Inbred C57BL
• NLR Family, Pyrin Domain-Containing 3 Protein (genetics)
• Staphylococcal Infections
• Staphylococcus aureus (metabolism)
• Toll-Like Receptor 2 (metabolism)
• Toll-Like Receptor 4 (genetics, metabolism)
• Tumor Necrosis Factor-alpha (metabolism)