4.7 Article

The important role of NLRP6 inflammasome in Pasteurella multocida infection

Journal

VETERINARY RESEARCH
Volume 53, Issue 1, Pages -

Publisher

BMC
DOI: 10.1186/s13567-022-01095-0

Keywords

Pasteurella multocida; NLRP6 inflammasome; IL-1 beta; NLRP3

Funding

  1. National Natural Science Foundation of China [32172850, 32102684]
  2. Fundamental Research Funds for the Central Universities [SWU120057]
  3. China Agriculture Research System of MOF and MARA [CARS37]
  4. Foundation for Innovation Research Group in Chongqing Universities [CXQT20004]

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In this study, the mechanism of P. multocida-induced NLRP6 inflammasome activation was investigated. It was found that Nlrp6 (-/-) mice were more susceptible to P. multocida infection and had higher bacterial burden in the lungs. NLRP6 was shown to regulate inflammatory cytokine secretion and mediate caspase-1 activation and ASC oligomerization, resulting in IL-1β secretion.
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-1 beta 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-1 beta 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.

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