Abstract
Pasteurella multocida is a zoonotic pathogen causing respiratory infection in different animal species such as cattle, sheep, pigs, chickens and humans. Inflammasome is a complex assembled by multiple proteins in the cytoplasm and plays an important role in the host defense against microbial infection. Bovine Pasteurella multocida type A (PmCQ2) infection induces NLRP3 inflammasome activation and IL-1β secretion, but the mechanism of PmCQ2-induced activation of NLRP3 inflammasome is still unknown. Therefore, the underlying mechanism was investigated in this study. The results showed that potassium efflux mediated PmCQ2-induced IL-1β secretion and blocking potassium efflux attenuated PmCQ2-induced caspase-1 activation and ASC oligomerization. Furthermore, NIMA-related kinase 7 (Nek7) was also involved in PmCQ2-induced caspase-1 activation and IL-1β secretion. In addition, PmCQ2 infection promoted Nek7-NLRP3 interaction, which is dependent on potassium efflux. In conclusion, our results indicate the critical role of potassium efflux and Nek7 in Pasteurella multocida-induced NLRP3 inflammasome activation, which provides useful information about Pasteurella multocida-induced host immune response.
Highlights
Pasteurella multocida (P. multocida) is a conditional pathogen that causes a variety of diseases and closely related to the outbreak of animal diseases (Kubatzky, 2012; Wilson and Ho, 2013; Guan et al, 2020)
The results showed that P. multocida induced NIMA-related kinase 7 (Nek7) binding to NLR Family Pyrin Domain Containing 3 (NLRP3) protein to regulate the activation of NLRP3 inflammasome, and associated speck like protein (ASC) was recruited to activate caspase-1, leading to the maturation and secretion of IL-1β, and this process depended on K+ efflux
These results suggest that K+ efflux is a necessary upstream signaling of PmCQ2-induced NLRP3 inflammasome activation, which induces ASC oligomerization and caspase-1 activation, leading to IL-1β
Summary
Pasteurella multocida (P. multocida) is a conditional pathogen that causes a variety of diseases and closely related to the outbreak of animal diseases (Kubatzky, 2012; Wilson and Ho, 2013; Guan et al, 2020). P. multocida is identified and classified as five capsular serogroups (serogroups A, B, D, E and F) (Townsend et al, 2001). These serotypes of P. multocida causes severe infections with different clinical symptoms in different animals. P. multocida of B and E serotypes infect cloven-hoofed animals including cattle and sheep, causing hemorrhagic septicemia. P. multocida of serotype A and F infection cause avian cholera. P. multocida of serotype D (a small amount of type A) cause infection in pigs or rabbits, leading to atrophic rhinitis (Wilkie et al, 2012). Type A P. multocida is one of the main pathogens of bovine respiratory syndrome leading to high morbidity and mortality, which brings big economic loss in
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