BtpB inhibits innate inflammatory responses in goat alveolar macrophages through the TLR/NF-κB pathway and NLRP3 inflammasome during Brucella infection

• Published in: Microbial pathogenesis Vol. 166; p. 105536
• Main Authors: Li, Junmei, Zhang, Guangdong, Zhi, Feijie, Zhai, Yunyi, Zhou, Dong, Chen, Huatao, Lin, Pengfei, Tang, Keqiong, Liu, Wei, Jin, Yaping, Wang, Aihua
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.05.2022
• Subjects: Brucella suis S2; BtpB; GAMs; NLRP3; TLR; GAMs; NLRP3; BtpB; TLR; Brucella suis S2
• ISSN: 0882-4010; 1096-1208
• DOI: 10.1016/j.micpath.2022.105536

Brucella species are infectious facultative intracellular pathogens. They have evolved multiple strategies to thwart immune responses and replicate in macrophages for chronic persistence in the host. As a Brucella effector, BtpB is transferred into target cells through the type IV secretion system. BtpB, a Toll/interleukin-1 receptor domain-containing protein, blocks host innate immune responses by interfering with Toll-like receptor signaling. However, the intracellular targets and their activated downstream pathways remain unclear. In this study, we constructed a strain of Brucella suis S2 with a deletion in the gene for BtpB, ΔbtpB, and the complemented strain, C-ΔbtpB with a restored copy of the btpB gene. The bacterial growth curves and stress resistance results showed that BtpB did not affect B. suis S2 growth. Infection of alveolar macrophages with WT and ΔbtpB strains showed that BtpB inhibited TLR2 and TLR4 expression and attenuated NLRP3 inflammasome activation. BtpB also attenuated secretion of the Brucella-induced proinflammatory cytokines, IL-1β, IL-6, and TNF-α, in alveolar macrophages while up-regulating IL-10 expression. In general, the results confirmed that BtpB specifically inhibits TLR2/TLR4 and disrupts NLRP3 signaling pathways to inhibit host immune responses in early Brucella infections. •BtpB inhibits Brucella-induced innate inflammatory responses.•BtpB inhibits TLR2 and TLR4 expression, and nuclear translocation of NF-κB during Brucella infection.•BtpB suppresses the formation of cellular ROS during Brucella infection.•BtpB inhibits NLRP3 inflammasome activation during early Brucella infection.