布鲁氏菌与宿主天然免疫信号通路相互作用的研究进展

doi:10.11843/j.issn.0366-6964.2025.04.009

摘要/Abstract

摘要：

布鲁氏菌病(brucellosis)是一种由布鲁氏菌(Brucella)感染引起的全球性人兽共患病。近年来，我国布鲁氏菌病防控形势严峻，对牛羊养殖业和公共卫生安全构成较大威胁。天然免疫是抵御病原微生物感染的第一道防线，对维持机体的稳态至关重要。布鲁氏菌能够通过多种策略调节天然免疫信号通路，从而建立持续性感染，也能引起关节炎、肝炎、脑炎、流产等炎症性疾病。全面深入理解布鲁氏菌与天然免疫信号通路相互作用机制，可以为研发安全高效的疫苗或药物提供新的思路。因此，本文综述了Toll样受体(Toll-like receptors，TLRs)、环鸟苷酸腺苷酸合成酶(cyclic guanosine adenylate synthetase，cGAS)、干扰素基因刺激因子(stimulator of interferon genes，STING)、NOD样受体(NOD-like receptors，NLRs)、AIM2样受体(AIM2-like receptors，ALRs)、C型凝集素受体(C-type lectin receptors，CLRs)和RIG-I样受体(RIG-I-like receptors，RLRs)等天然免疫信号通路在抵御布鲁氏菌感染中的作用及机制，并总结了布鲁氏菌逃逸或劫持这些信号通路的策略。

关键词: 布鲁氏菌, 免疫逃逸, Toll样受体, 环鸟苷酸腺苷酸合成酶, 干扰素基因刺激因子, NOD样受体, AIM2样受体, C型凝集素受体, RIG-I样受体

Abstract:

Brucellosis is a global zoonosis caused by Brucella infection. In recent years, the situation of brucellosis prevention and control is grim in China, posing a great threat to the cattle and sheep farming industry and public health security. Innate immunity serves as the first line of defense against pathogenic mocrobial infections and is crucial for maintaining homeostasis of the organism. Brucella can modulate innate immunity signaling pathways through a variety of strategies to establish persistent infections and also cause inflammatory diseases such as arthritis, hepatitis, encephalitis, and abortion. A comprehensive and in-depth understanding of the molecular mechanisms of Brucella interactions with innate immunity signaling pathways may provide new ideas for the development of safe and effective vaccines or drugs. Therefore, this paper reviews the roles and mechanisms of innate immunity signaling pathways such as Toll-like receptors(TLRs), cyclic guanosine adenylate synthetase(cGAS), stimulator of interferon genes(STING), NOD-like receptors(NLRs), AIM2-like receptors(ALRs), C-type lectin receptors(CLRs) and RIG-I-like receptors(RLRs) in the defense against Brucella infections, and summarizes the strategies of Brucella evade or hijacking these signaling pathways.

Key words: Brucella, immune envasion, TLRs, cGAS, STING, NLRs, ALRs, CLRs, RLRs

中图分类号:

S852.614

刘爱军, 黄晓兵, 张传亮, 张红丽. 布鲁氏菌与宿主天然免疫信号通路相互作用的研究进展[J]. 畜牧兽医学报, 2025, 56(4): 1561-1574.

LIU Aijun, HUANG Xiaobing, ZHANG Chuanliang, ZHANG Hongli. Progress on the Interactions of Brucella with Host Innate Immunity Signaling Pathways[J]. Acta Veterinaria et Zootechnica Sinica, 2025, 56(4): 1561-1574.

图/表 3

表 1

天然免疫信号在小鼠布鲁氏菌感染中的作用"

受体 Receptor	配体 Ligand	感染途径 Route of infection	作用 Function
TLR2	脂蛋白^[15]	腹腔注射	TLR2^-/-小鼠B. microti、B. abortus易感性均无显著差异^[22-23,27]
		气管内注射	TLR2^-/-小鼠肺泡巨噬细胞B. abortus负荷增高^[28]
TLR4	LPS和Omp16^[15]	腹腔注射	TLR4^-/-小鼠B. microti、B. abortus易感性无显著差异^[23,27]，TLR2/4^-/-小鼠B. microti清除延迟^[27]
TLR3/7	RNA^[16]	腹腔注射	TLR3^-/-和TLR7^-/-小鼠B. abortus易感性均无显著差异^[16]
TLR6	脂蛋白^[15]	腹腔注射	TLR6^-/-小鼠B. abortus易感性增加^[22]
TLR9	DNA^[18-19]	腹腔注射	TLR9^-/-小鼠B. abortus感染初期易感性增加^[18]
cGAS	DNA^[44]	气管内注射	cGAS^-/-小鼠B. abortus易感性增加^[43]
		腹腔注射	cGAS^-/-小鼠B. abortus易感性无显著性差异^[44]
STING	c-diGMP和DNA^[44]	气管内注射	STING^-/-小鼠B. abortus易感性增加^[43]
		腹腔注射	STING^-/-小鼠B. abortus易感性增加^[44]
NLRP3	DAMPs^[63]	气管内注射	NLRP3^-/-小鼠B. abortus易感性增加^[64]
		腹腔注射	NLRP3^-/-小鼠B. abortus易感性增加^[65]，肝脏纤维化减少^[72]，脑炎减轻^[15]
AIM2	DNA^[62]	腹腔注射	AIM2^-/-小鼠B. abortus易感性增加^[62,65]，肝脏纤维化减少^[72]，脑炎减轻^[15]
		气管内注射	AIM2^-/-小鼠B. abortus易感性增加^[64]
NLRP6	尚不清楚	口服感染	NLRP6^-/-小鼠对B. abortus感染抵抗力增加^[75]
		腹腔注射	NLRP6^-/-小鼠B. abortus易感性无显著差异^[75]
NLRP12	尚不清楚	腹腔注射	NLRP12^-/-小鼠对B. abortus感染抵抗力增加^[76]
NOD1/2	尚不清楚	腹腔注射	NOD1^-/-和NOD2^-/-小鼠B. abortus易感性无显著差异^[78]
NLRC4	鞭毛蛋白^[31]	腹腔注射	NLRC4^-/-小鼠B. melitensis易感性增加^[31]
CASP11	LPS^[61]	腹腔注射	CASP11^-/-小鼠B. abortus易感性增加^[59] CASP11^-/-小鼠B. abortus感染存活率无显著差异，脾脏细菌负荷减少^[60]

表 1

图 1

图 2

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