TY - JOUR
T1 - NLRP3 inflammasome activation contributes to Listeria monocytogenes-induced animal pregnancy failure
AU - Li, Wenyan
AU - Chang, Yumei
AU - Liang, Shuang
AU - Zhong, Zhenyu
AU - Li, Xiujin
AU - Wen, Jiexia
AU - Zhang, Yonghong
AU - Zhang, Jianlou
AU - Wang, Liyue
AU - Lin, Hongyu
AU - Cao, Xuebin
AU - Huang, Heling
AU - Zhong, Fei
N1 - Funding Information:
WL and YC performed the major experiments, analyzed the data and wrote the partial draft of the manuscript. SL, ZZ and XL designed partial study plan and revised the manuscript. JW, LW, HL, JZ, YZ provided technical assistance and participated partial experiments. XC and HH directed partial study and acquired the funding, FZ conceived the study, generated the working hypothesis, designed the study plan, obtained financial support, revised the draft and wrote the final version of the manuscript. All authors read and approved the final manuscript.
Publisher Copyright:
© 2016 Li et al.
PY - 2016/2/24
Y1 - 2016/2/24
N2 - 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.
AB - 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.
KW - Inflammasome
KW - Listeria monocytogenes
KW - Listeriolysin O
KW - NLRP3
KW - Pregnancy failure
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UR - http://www.scopus.com/inward/citedby.url?scp=84959154064&partnerID=8YFLogxK
U2 - 10.1186/s12917-016-0655-2
DO - 10.1186/s12917-016-0655-2
M3 - Article
C2 - 26911557
AN - SCOPUS:84959154064
SN - 1746-6148
VL - 12
JO - BMC Veterinary Research
JF - BMC Veterinary Research
IS - 1
M1 - 36
ER -