NLRP3 inflammasome activation contributes to Listeria monocytogenes-induced animal pregnancy failure

BMC Veterinary Research

Research Article

Xiujin Li¹  Xuebin Cao²  Heling Huang²  Yumei Chang²  Shuang Liang³  Zhenyu Zhong⁴  Jiexia Wen⁵  Liyue Wang⁵  Fei Zhong⁵  Jianlou Zhang⁵  Yonghong Zhang⁵  Wenyan Li⁶  Hongyu Lin⁷ 

[1] Department of Biotechnology, College of Environmental and Chemical Engineering, Yanshan University, 066004, Qinhuangdao, China;Department of Gynaecology and Obstetrics, 252 Hospital of Chinese PLA, 071000, Baoding, China;Department of Medicine, School of Medicine, University of California San Diego, 92093, La Jolla, CA, USA;Department of Pharmacology, School of Medicine, University of California San Diego, 92093, La Jolla, CA, USA;Laboratory of Molecular Virology and Immunology, College of Veterinary Medicine, Agricultural University of Hebei; Hebei Engineering and Technology Research Center of Veterinary Biotechnology, 071000, Baoding, China;Laboratory of Molecular Virology and Immunology, College of Veterinary Medicine, Agricultural University of Hebei; Hebei Engineering and Technology Research Center of Veterinary Biotechnology, 071000, Baoding, China;Department of Biology, School of Medicine, Hebei University, 071000, Baoding, China;Laboratory of Molecular Virology and Immunology, College of Veterinary Medicine, Agricultural University of Hebei; Hebei Engineering and Technology Research Center of Veterinary Biotechnology, 071000, Baoding, China;Department of Biotechnology, College of Environmental and Chemical Engineering, Yanshan University, 066004, Qinhuangdao, China;

关键词: Listeria monocytogenes;    Listeriolysin O;    Pregnancy failure;    Inflammasome;    NLRP3;   

DOI  :  10.1186/s12917-016-0655-2

 received in 2015-06-02, accepted in 2016-02-15,  发布年份 2016

来源: Springer

【 摘 要 】

BackgroundListeria monocytogenes (LM), a foodborne pathogen, can cause pregnancy failure in animals, especially in ruminants. Recent studies have shown that LM activates inflammasomes to induce IL-1β release in macrophages, however, whether the inflammasome activation regulates LM-induced pregnancy failure remains largely unknown. Here we used mouse model to investigate the molecular mechanism by which LM-induced inflammsome activation contributes to LM-associated pregnancy failureResultsWe showed that wild-type, but not Listeriolysin O-deficient (Δhly) LM, significantly reduced mouse embryo survival, accompanied by the increase of IL-1β release and caspase-1 activation. IL-1β neutralization significantly reduced the LM-induced embryo losses, suggesting that LM-induced pregnancy failure was associated with LLO-induced inflammasome activation. To dissect the inflammasome sensor and components responsible for LM-induced caspase-1 activation and IL-1β production, we used wild-type and NLRP3−/−, AIM2−/−, NLRC4−/−, ASC−/−, caspase-1−/− and cathepsin B−/− mouse macrophages to test the roles of these molecules in LM-induce IL-1β production. We found that NLRP3 inflammasome was the main pathway in LM-induced caspase-1 activation and IL-1β production. To explore the mechanism of LM-induced pregnancy failure, we investigated the effects of LM-infected macrophages on SM9-1 mouse trophoblasts. We found that the conditioned medium from LM-infected-macrophage or the recombinant IL-1β significantly up-regulated TNFα, IL-6 and IL-8 productions in trophoblasts, suggesting that the LM-induced macrophage inflammasome activation increased trophoblast pro-inflammatory cytokine production, which was adverse to the animal pregnancy maintenance.ConclusionsOur data demonstrated that the LLO-induced NLRP3 inflammasome activation plays a key role in LM-induced pregnancy failure, and inflammasome-mediated macrophage dysregulation on trophoblasts might be involved in the pregnancy failure.

【 授权许可】

CC BY   
© Li et al. 2016