High- and low-virulent bovine Pasteurella multocida induced differential NLRP3 inflammasome activation and subsequent IL-1β secretion

Abstract

Pasteurella multocida is a gram-negative bacterial pathogen, which causes a large number of diseases in mammals, birds and human. Although the bacterium has been known for decades, the pathogenesis and the mechanisms of P. multocida induced host immunity are poorly understood. Recently, we have reported that nucleotide-binding oligomerization domain-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome plays an important role in caspase-1 activation and IL-1β secretion in macrophages infected with P. multocida. In this study, the inflammasome activation and IL-1β secretion were further demonstrated by using high- and low-virulent bovine P. multocida isolates. The results showed that, comparing with macrophages infected with the high-virulent PmCQ2 isolates, the low-virulent PmCQ6 induced higher levels of NLRP3 transcription, caspase-1 activation and mature IL-1β secretion. Furthermore, the capsule of the high-virulent PmCQ2 was much thicker than that of low-virulent PmCQ6, which indicating that capsular thickness might influence the bacteria colonization and NLRP3 inflammasome activation. The results suggested that differences in maturation of IL-1β in macrophages upon high- and low- virulent P. multocida infection are critically dependent on the differential activation of NLRP3 inflammasome. This study provided more understanding for the host immune responses induced by P. multocida and further extended the knowledge of P. multocida virulence from the view of host innate immunity.