title: Porcine reproductive and respiratory syndrome virus induces IL-1β production depending on TLR4/MyD88 pathway and NLRP3 inflammasome in primary porcine alveolar macrophages.
abstract: Porcine reproductive and respiratory syndrome virus (PRRSV) is an Arterivirus that has been devastating the swine industry worldwide since the late 1980s. Previous studies have reported that PRRSV infection induced the production of IL-1 β . However, the cellular sensors and signaling pathways involved in this process have not been elucidated yet. Here, we studied the mechanisms responsible for the production of IL-1 β in response to highly pathogenic PRRSV. Upon PRRSV infection of primary porcine alveolar macrophages, both mRNA expression and secretion of IL-1 β were significantly increased in a time- and dose-dependent manner. We also investigated the role of several pattern-recognition receptors and adaptor molecules in this response and showed that the TLR4/MyD88 pathway and its downstream signaling molecules, NF- κ B, ERK1/2, and p38 MAPKs, were involved in IL-1 β production during PRRSV infection. Treatment with specific inhibitors or siRNA knockdown assays demonstrated that components of the NLRP3 inflammasome were crucial for IL-1 β secretion but not for IL-1 β mRNA expression. Furthermore, TLR4/MyD88/NF- κ B signaling pathway was involved in PRRSV-induced expression of NLRP3 inflammasome components. Together, our results deciphered the pathways leading from recognition of PRRSV to the production and release of IL-1 β , providing a deeper knowledge of the mechanisms of PRRSV-induced inflammation responses.
authors: State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China ; Department of Immunology and Aetology, College of Basic Medicine, Hubei University of Chinese Medicine, Wuhan 430065, China.
authors: Jing
authors: J
authors: Bi
authors: State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China.
authors: Shuang
authors: S
authors: Song
authors: State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China.
authors: Liurong
authors: L
authors: Fang
authors: State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China.
authors: Dang
authors: D
authors: Wang
authors: State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China.
authors: Huiyuan
authors: H
authors: Jing
authors: State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China.
authors: Li
authors: L
authors: Gao
authors: State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China.
authors: Yidong
authors: Y
authors: Cai
authors: State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China.
authors: Rui
authors: R
authors: Luo
authors: State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China.
authors: Huanchun
authors: H
authors: Chen
authors: State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China ; Laboratory of Infectious Diseases, College of Veterinary Medicine, Huazhong Agricultural University, 1 Shizishan Street, Wuhan 430070, China.
authors: Shaobo
authors: S
authors: Xiao
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism*; D058847:Inflammasomes / Q000378:metabolism*; D007249:Inflammation; D053583:Interleukin-1beta / Q000378:metabolism*; D007700:Kinetics; D016676:Macrophages, Alveolar / Q000166:cytology / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D019318:Porcine Reproductive and Respiratory Syndrome / Q000276:immunology* / Q000378:metabolism; D019316:Porcine respiratory and reproductive syndrome virus / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000378:metabolism; D015398:Signal Transduction; D013552:Swine; D051197:Toll-Like Receptor 4 / Q000378:metabolism*
chemical_list: D002352:Carrier Proteins; D058847:Inflammasomes; D053583:Interleukin-1beta; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C453881:NLRP3 protein, human; D034741:RNA, Small Interfering; D051197:Toll-Like Receptor 4