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

Author:
Li, Wenyan, Chang, Yumei, Liang, Shuang, Zhong, Zhenyu, Li, Xiujin, Wen, Jiexia, Zhang, Yonghong, Zhang, Jianlou, Wang, Liyue, Lin, Hongyu, Cao, Xuebin, Huang, Heling, Zhong, Fei
Source:
BMC veterinary research 2016 v.12 no.1 pp. 36
ISSN:
1746-6148
Subject:
Listeria monocytogenes, animal models, caspase-1, cathepsins, food pathogens, interleukin-1beta, interleukin-6, interleukin-8, macrophages, mice, neutralization, pregnancy, ruminants, trophoblast, tumor necrosis factor-alpha
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.
Agid:
5485242