PMID- 35811022 OWN - NLM STAT- MEDLINE DCOM- 20220809 LR - 20220809 IS - 1096-1208 (Electronic) IS - 0882-4010 (Linking) VI - 169 DP - 2022 Aug TI - TLR2, TLR4, and NLRP3 mediated the balance between host immune-driven resistance and tolerance in Staphylococcus aureus-infected mice. PG - 105671 LID - S0882-4010(22)00284-4 [pii] LID - 10.1016/j.micpath.2022.105671 [doi] AB - 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-alpha), 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-alpha), 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. CI - Copyright (c) 2022 Elsevier Ltd. All rights reserved. FAU - Gong, Zhiguo AU - Gong Z AD - Laboratory of Veterinary Clinical Pharmacology, College of Veterinary Medicine, Inner Mongolia Agricultural University, No. 306, Zhaowuda Road, Saihan District, 010018, Hohhot, China; Key Laboratory of Clinical Diagnosis and Treatment Techniques for Animal Disease, Ministry of Agriculture, Inner Mongolia Agricultural University, Hohhot, China. FAU - Zhang, Jing AU - Zhang J AD - Laboratory of Veterinary Clinical Pharmacology, College of Veterinary Medicine, Inner Mongolia Agricultural University, No. 306, Zhaowuda Road, Saihan District, 010018, Hohhot, China; Key Laboratory of Clinical Diagnosis and Treatment Techniques for Animal Disease, Ministry of Agriculture, Inner Mongolia Agricultural University, Hohhot, China. FAU - Zhang, Shuangyi AU - Zhang S AD - Laboratory of Veterinary Clinical Pharmacology, College of Veterinary Medicine, Inner Mongolia Agricultural University, No. 306, Zhaowuda Road, Saihan District, 010018, Hohhot, China; Key Laboratory of Clinical Diagnosis and Treatment Techniques for Animal Disease, Ministry of Agriculture, Inner Mongolia Agricultural University, Hohhot, China. FAU - Cao, Jinshan AU - Cao J AD - Laboratory of Veterinary Clinical Pharmacology, College of Veterinary Medicine, Inner Mongolia Agricultural University, No. 306, Zhaowuda Road, Saihan District, 010018, Hohhot, China; Key Laboratory of Clinical Diagnosis and Treatment Techniques for Animal Disease, Ministry of Agriculture, Inner Mongolia Agricultural University, Hohhot, China. FAU - Fu, Yunhe AU - Fu Y AD - Department of Clinical Veterinary Medicine, College of Veterinary Medicine, Jilin University, NO.5333, Xian Road, Lvyuan District, 130062, Changchun, China. FAU - Hu, Xiaoyu AU - Hu X AD - Department of Clinical Veterinary Medicine, College of Veterinary Medicine, Jilin University, NO.5333, Xian Road, Lvyuan District, 130062, Changchun, China. FAU - Zhao, Jiamin AU - Zhao J AD - Laboratory of Veterinary Clinical Pharmacology, College of Veterinary Medicine, Inner Mongolia Agricultural University, No. 306, Zhaowuda Road, Saihan District, 010018, Hohhot, China; Key Laboratory of Clinical Diagnosis and Treatment Techniques for Animal Disease, Ministry of Agriculture, Inner Mongolia Agricultural University, Hohhot, China. FAU - Gu, Baichen AU - Gu B AD - Laboratory of Veterinary Clinical Pharmacology, College of Veterinary Medicine, Inner Mongolia Agricultural University, No. 306, Zhaowuda Road, Saihan District, 010018, Hohhot, China; Key Laboratory of Clinical Diagnosis and Treatment Techniques for Animal Disease, Ministry of Agriculture, Inner Mongolia Agricultural University, Hohhot, China. FAU - Li, Qianru AU - Li Q AD - Laboratory of Veterinary Clinical Pharmacology, College of Veterinary Medicine, Inner Mongolia Agricultural University, No. 306, Zhaowuda Road, Saihan District, 010018, Hohhot, China; Key Laboratory of Clinical Diagnosis and Treatment Techniques for Animal Disease, Ministry of Agriculture, Inner Mongolia Agricultural University, Hohhot, China. FAU - Zhang, Kai AU - Zhang K AD - Laboratory of Veterinary Clinical Pharmacology, College of Veterinary Medicine, Inner Mongolia Agricultural University, No. 306, Zhaowuda Road, Saihan District, 010018, Hohhot, China; Key Laboratory of Clinical Diagnosis and Treatment Techniques for Animal Disease, Ministry of Agriculture, Inner Mongolia Agricultural University, Hohhot, China. FAU - Ren, Peipei AU - Ren P AD - Laboratory of Veterinary Clinical Pharmacology, College of Veterinary Medicine, Inner Mongolia Agricultural University, No. 306, Zhaowuda Road, Saihan District, 010018, Hohhot, China; Key Laboratory of Clinical Diagnosis and Treatment Techniques for Animal Disease, Ministry of Agriculture, Inner Mongolia Agricultural University, Hohhot, China. FAU - Liu, Bo AU - Liu B AD - Laboratory of Veterinary Clinical Pharmacology, College of Veterinary Medicine, Inner Mongolia Agricultural University, No. 306, Zhaowuda Road, Saihan District, 010018, Hohhot, China; Key Laboratory of Clinical Diagnosis and Treatment Techniques for Animal Disease, Ministry of Agriculture, Inner Mongolia Agricultural University, Hohhot, China. Electronic address: liubo8510@imau.edu.cn. FAU - Mao, Wei AU - Mao W AD - Laboratory of Veterinary Clinical Pharmacology, College of Veterinary Medicine, Inner Mongolia Agricultural University, No. 306, Zhaowuda Road, Saihan District, 010018, Hohhot, China; Key Laboratory of Clinical Diagnosis and Treatment Techniques for Animal Disease, Ministry of Agriculture, Inner Mongolia Agricultural University, Hohhot, China. Electronic address: maowei2014@imau.edu.cn. LA - eng PT - Journal Article DEP - 20220708 PL - England TA - Microb Pathog JT - Microbial pathogenesis JID - 8606191 RN - 0 (Chemokine CCL5) RN - 0 (Cytokines) RN - 0 (HMGB1 Protein) RN - 0 (NLR Family, Pyrin Domain-Containing 3 Protein) RN - 0 (Nlrp3 protein, mouse) RN - 0 (Tlr2 protein, mouse) RN - 0 (Tlr4 protein, mouse) RN - 0 (Toll-Like Receptor 2) RN - 0 (Toll-Like Receptor 4) RN - 0 (Tumor Necrosis Factor-alpha) RN - 130068-27-8 (Interleukin-10) SB - IM MH - Animals MH - Chemokine CCL5 MH - Cytokines MH - *HMGB1 Protein MH - Interleukin-10 MH - Mammals/metabolism MH - Mice MH - Mice, Inbred C57BL MH - NLR Family, Pyrin Domain-Containing 3 Protein/genetics MH - *Staphylococcal Infections MH - Staphylococcus aureus/metabolism MH - Toll-Like Receptor 2/metabolism MH - Toll-Like Receptor 4/genetics/metabolism MH - Tumor Necrosis Factor-alpha/metabolism OTO - NOTNLM OT - Immune-driven resistance and tolerance OT - NLRP3 OT - Staphylococcus aureus OT - TLR2 OT - TLR4 EDAT- 2022/07/11 06:00 MHDA- 2022/08/10 06:00 CRDT- 2022/07/10 19:27 PHST- 2022/01/03 00:00 [received] PHST- 2022/06/15 00:00 [revised] PHST- 2022/07/05 00:00 [accepted] PHST- 2022/07/11 06:00 [pubmed] PHST- 2022/08/10 06:00 [medline] PHST- 2022/07/10 19:27 [entrez] AID - S0882-4010(22)00284-4 [pii] AID - 10.1016/j.micpath.2022.105671 [doi] PST - ppublish SO - Microb Pathog. 2022 Aug;169:105671. doi: 10.1016/j.micpath.2022.105671. Epub 2022 Jul 8.