title: NLRP3 inflammasome activation contributes to Listeria monocytogenes-induced animal pregnancy failure.
abstract: BACKGROUND
  Listeria 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 failure
  
  
  RESULTS
  We 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.
  
  
  CONCLUSIONS
  Our 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.
authors.affiliation: Laboratory of Molecular Virology and Immunology, College of Veterinary Medicine, Agricultural University of Hebei; Hebei Engineering and Technology Research Center of Veterinary Biotechnology, Baoding, 071000, China. liwenyan358@sohu.com.|Department of Biology, School of Medicine, Hebei University, Baoding, 071000, China. liwenyan358@sohu.com.
authors.forename: Wenyan
authors.initials: W
authors.lastname: Li
authors.affiliation: Department of Gynaecology and Obstetrics, 252 Hospital of Chinese PLA, Baoding, 071000, China. 253880121@qq.com.
authors.forename: Yumei
authors.initials: Y
authors.lastname: Chang
authors.affiliation: Department of Medicine, School of Medicine, University of California San Diego, La Jolla, CA, 92093, USA. shl067@ucsd.edu.
authors.forename: Shuang
authors.initials: S
authors.lastname: Liang
authors.affiliation: Department of Pharmacology, School of Medicine, University of California San Diego, La Jolla, CA, 92093, USA. z8zhong@ucsd.edu.
authors.forename: Zhenyu
authors.initials: Z
authors.lastname: Zhong
authors.affiliation: Department of Biotechnology, College of Environmental and Chemical Engineering, Yanshan University, Qinhuangdao, 066004, China. lixiujin9824@aliyun.com.
authors.forename: Xiujin
authors.initials: X
authors.lastname: Li
authors.affiliation: Laboratory of Molecular Virology and Immunology, College of Veterinary Medicine, Agricultural University of Hebei; Hebei Engineering and Technology Research Center of Veterinary Biotechnology, Baoding, 071000, China. wenjiexia2010@163.com.
authors.forename: Jiexia
authors.initials: J
authors.lastname: Wen
authors.affiliation: Laboratory of Molecular Virology and Immunology, College of Veterinary Medicine, Agricultural University of Hebei; Hebei Engineering and Technology Research Center of Veterinary Biotechnology, Baoding, 071000, China. zhangyonghong@163.com.
authors.forename: Yonghong
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Laboratory of Molecular Virology and Immunology, College of Veterinary Medicine, Agricultural University of Hebei; Hebei Engineering and Technology Research Center of Veterinary Biotechnology, Baoding, 071000, China. zhangjianlou1106@126.com.
authors.forename: Jianlou
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Laboratory of Molecular Virology and Immunology, College of Veterinary Medicine, Agricultural University of Hebei; Hebei Engineering and Technology Research Center of Veterinary Biotechnology, Baoding, 071000, China. wangliyue1989@163.com.
authors.forename: Liyue
authors.initials: L
authors.lastname: Wang
authors.affiliation: Laboratory of Molecular Virology and Immunology, College of Veterinary Medicine, Agricultural University of Hebei; Hebei Engineering and Technology Research Center of Veterinary Biotechnology, Baoding, 071000, China. hymumu@163.com.|Department of Biotechnology, College of Environmental and Chemical Engineering, Yanshan University, Qinhuangdao, 066004, China. hymumu@163.com.
authors.forename: Hongyu
authors.initials: H
authors.lastname: Lin
authors.affiliation: Department of Gynaecology and Obstetrics, 252 Hospital of Chinese PLA, Baoding, 071000, China. caoxb252@163.com.
authors.forename: Xuebin
authors.initials: X
authors.lastname: Cao
authors.affiliation: Department of Gynaecology and Obstetrics, 252 Hospital of Chinese PLA, Baoding, 071000, China. HHL252@aliyun.com.
authors.forename: Heling
authors.initials: H
authors.lastname: Huang
authors.affiliation: Laboratory of Molecular Virology and Immunology, College of Veterinary Medicine, Agricultural University of Hebei; Hebei Engineering and Technology Research Center of Veterinary Biotechnology, Baoding, 071000, China. zhongf@hebau.edu.cn.
authors.forename: Fei
authors.initials: F
authors.lastname: Zhong
mesh_terms: D000022:Abortion, Spontaneous / Q000382:microbiology*; D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism*; D002478:Cells, Cultured; D005260:Female; D058847:Inflammasomes; D053583:Interleukin-1beta / Q000378:metabolism; D008089:Listeria monocytogenes / Q000472:pathogenicity*; D008088:Listeriosis / Q000150:complications* / Q000378:metabolism / Q000473:pathology; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000382:microbiology*; D014327:Trophoblasts
chemical_list: D002352:Carrier Proteins; D058847:Inflammasomes; D053583:Interleukin-1beta; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C492716:Nlrp3 protein, mouse