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The important role of NLRP6 inflammasome in Pasteurella multocida infection
Ist Teil von
Veterinary research (Paris), 2022-10, Vol.53 (1), p.1-81, Article 81
Ort / Verlag
London: BioMed Central Ltd
Erscheinungsjahr
2022
Quelle
EZB Electronic Journals Library
Beschreibungen/Notizen
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-1β 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 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
.