| Title: | The important role of NLRP6 inflammasome in Pasteurella multocida infection |
| Author(s): | Wu X; Zeng Z; Tian H; Peng L; Xu D; Wang Y; Ye C; Peng Y; Fang R; |
| Address: | "Joint International Research Laboratory of Animal Health and Animal Food Safety, College of Veterinary Medicine, Southwest University, Chongqing, 400715, China. Chongqing Centers for Disease Control and Prevention, Chongqing, 401120, China. Joint International Research Laboratory of Animal Health and Animal Food Safety, College of Veterinary Medicine, Southwest University, Chongqing, 400715, China. pyy2002@sina.com. Joint International Research Laboratory of Animal Health and Animal Food Safety, College of Veterinary Medicine, Southwest University, Chongqing, 400715, China. rdfang@swu.edu.cn. Immunology Research Center, Medical Research Institute, Southwest University, Chongqing, 402460, China. rdfang@swu.edu.cn. Chongqing Key Laboratory of Herbivore Science, Chongqing, 400715, China. rdfang@swu.edu.cn" |
| DOI: | 10.1186/s13567-022-01095-0 |
| ISSN/ISBN: | 1297-9716 (Electronic) 0928-4249 (Print) 0928-4249 (Linking) |
| Abstract: | "Pasteurella multocida (P. multocida) can cause severe respiratory disease in cattle, resulting in high mortality and morbidity. Inflammasomes are multiprotein complexes in the cytoplasm that recognize pathogens and play an important role in the host defense against microbial infection. In this study, the mechanism of P. multocida-induced NLRP6 inflammasome activation was investigated in vitro and in vivo. Firstly, P. multocida induced severe inflammation with a large number of inflammatory cells infiltrating the lungs of WT and Nlrp6(-/-) mice. Nlrp6(-/-) mice were more susceptible to P. multocida infection and they had more bacterial burden in the lungs. Then, the recruitment of macrophages and neutrophils in the lungs was investigated and the results show that the number of immune cells was significantly decreased in Nlrp6(-/-) mice. Subsequently, NLRP6 was shown to regulate P. multocida-induced inflammatory cytokine secretion including IL-1beta and IL-6 both in vivo and in vitro while TNF-alpha secretion was not altered. Moreover, NLRP6 was found to mediate caspase-1 activation and ASC oligomerization, resulting in IL-1beta secretion. Furthermore, NLRP6 inflammasome mediated the gene expression of chemokines including CXCL1, CXCL2 and CXCR2 which drive the activation of NLRP3 inflammasomes. Finally, NLRP3 protein expression was detected to be abrogated in P. multocida-infected Nlrp6(-/-) macrophages, indicating the synergic effect of NLRP6 and NLRP3. Our study demonstrates that NLRP6 inflammasome plays an important role in the host against P. multocida infection and contributes to the development of immune therapeutics against P. multocida" |
| Keywords: | "Animals Caspase 1 Caspases *Inflammasomes Interleukin-1beta/metabolism Interleukin-6 Mice Mice, Inbred C57BL NLR Family, Pyrin Domain-Containing 3 Protein/metabolism *Pasteurella multocida Receptors, Cell Surface/*metabolism Tumor Necrosis Factor-alpha IL;" |
| Notes: | "MedlineWu, Xingping Zeng, Zheng Tian, Hongliang Peng, Lianci Xu, Dongyi Wang, Yu Ye, Chao Peng, Yuanyi Fang, Rendong eng 32172850/National Natural Science Foundation of China/ 32102684/National Natural Science Foundation of China/ SWU120057/Fundamental Research Funds for the Central Universities/ England 2022/10/13 Vet Res. 2022 Oct 12; 53(1):81. doi: 10.1186/s13567-022-01095-0" |
