Polyamine Transport Protein PotD Protects Mice against Haemophilus parasuis and Elevates the Secretion of Pro-Inflammatory Cytokines of Macrophage via JNK-MAPK and NF-κB Signal Pathways through TLR4

多胺转运蛋白 PotD 通过 TLR4 介导 JNK-MAPK 和 NF-κB 信号通路保护小鼠免受副猪嗜血杆菌感染并促进巨噬细胞促炎细胞因子的分泌

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作者:Ke Dai, Xiaoyu Ma, Zhen Yang, Yung-Fu Chang, Sanjie Cao, Qin Zhao, Xiaobo Huang, Rui Wu, Yong Huang, Qigui Yan, Xinfeng Han, Xiaoping Ma, Xintian Wen, Yiping Wen

Abstract

The potD gene, belonging to the well-conserved ABC (ATP-binding cassette) transport system potABCD, encodes the bacterial substrate-binding subunit of the polyamine transport system. In this study, we found PotD in Haemophilus (Glaesserella) parasuis could actively stimulate both humoral immune and cellular immune responses and elevate lymphocyte proliferation, thus eliciting a Th1-type immune response in a murine immunity and infection model. Stimulation of Raw 264.7 macrophages with PotD validated that Toll-like receptor 4, rather than 2, participated in the positive transcription and expression of pro-inflammatory cytokines IL-1β, IL-6, and TNF-α using qPCR and ELISA. Blocking signal-regulated JNK-MAPK and RelA(p65) pathways significantly decreased PotD-induced pro-inflammatory cytokine production. Overall, we conclude that vaccination of PotD could induce both humoral and cellular immune responses and provide immunoprotection against H. parasuis challenge. The data also suggest that Glaesserella PotD is a novel pro-inflammatory mediator and induces TLR4-dependent pro-inflammatory activity in Raw 264.7 macrophages through JNK-MAPK and RelA(p65) pathways.

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