The important role of NLRP6 inflammasome in Pasteurella multocida infection

In this study, the mechanism ofP. 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 andNlrp6−/− mice.Nlrp6−/− mice were more susceptible toP. 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 inNlrp6−/− mice. Subsequently, NLRP6 was shown to regulateP. multocida-induced inflammatory cytokine secretion including IL-1 β and IL-6 both in vivo and in vitro while TNF-α secretion was not altered. Moreover, NLRP6 was found to mediate caspase-1 activation and ASC oligomerization, resulting in IL-1β 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 inP. multocida-infectedNlrp6−/− macrophages, indicating the synergic effect of NLRP6 and NLRP3. Our study demonstrates that NLRP6 inflammasome plays an important role in the host againstP. multocida infection and contributes to the development of immune therapeutics againstP. multocida.

Source: Veterinary Research - October 12, 2022 Category: Veterinary Research Source Type: research