NLRP3 mediates trophoblastic inflammasome activation and protects against Listeria monocytogenes infection during pregnancy

Gao, Yu1; Zhou, Min2,3; Zhang, Wen4; Jiang, Jinxing5; Ouyang, Zhibin5; Zhu, Yuanfan6,7; Li, Nini8,9

2022-10-01

10.21037/atm-22-4120

Annals of Translational Medicine   Impact Factor & Quartile

2305-5839

2305-5847

Background: Intrauterine Listeria monocytogenes (L. monocytogenes) infections pose a major threat during pregnancy via affecting placental immune responses. However, the underlying mechanisms of placental defense against this pathogen remain ill-defined. Therefore, this study aims to investigate the function and the mechanism of inflammasomes on against L. monocytogenes infection during pregnancy.Methods: A listeriosis murine model and cell culture system was used to investigate the role of trophoblastic nucleotide-binding oligomerization domain-like receptor pyrin domain-containing 3 (NLRP3) in orchestrating innate immune responses to L. monocytogenes infection. Caspase-1 activity was determined using a caspase-1 activity colorimetric kit. NLRP3 and apoptosis-associated speck-like protein containing a CARD (ASC) in placental tissue was detected by immunohistochemistry. NLRP3 in HTR-8/SVneo cells was also detected by immunofluorescence. The expression of interleukin 113 (IL-113), NLRP3, ASC, and caspase-1 was detected by Western blot. We characterized the NLRP3 inflammasome in trophoblast cells according to whether L. monocytogenes infection increased the activation of caspase-1 and the release of IL-113. For human or mouse IL-113 in the culture supernatants and mouse tissue lysates were analyzed using ELISA Kits.Results: Trophoblast cells constitutively expressed the components of the NLRP3 inflammasome. In vitro, L. monocytogenes triggers NLRP3 inflammasome activation in trophoblast cells by inducing caspase-1 activation, increasing the NLRP3 protein levels, IL-113 maturation and secretion in HTR-8/SVneo cells. In vivo, L. monocytogenes induces fetal resorption and IL-113 processing in pregnant mice. In addition, NLRP3-deficient mice were more prone to fetal loss than their wild-type counterparts following infection with L. monocytogenes at a lower infective doseConclusions: We conclude that trophoblast cells respond to L. monocytogenes infection through the NLRP3 receptor, resulting in inflammasome activation and IL-113 production, which prevents listeriosis during pregnancy.

Pregnancy trophoblast Listeria monocytogenes (L monocytogenes) inflammasome nucleotide-binding oligomerization domain-like receptor pyrin domain-containing 3 (NLRP3)

SCI

English

Corresponding

[2019A1515011068] ; [JCYJ20210324114009026]

Oncology ; Research & Experimental Medicine

Oncology ; Medicine, Research & Experimental

WOS:000887090000001

AME PUBLISHING COMPANY

Web of Science

1.Jinan Univ, Shenzhen Peoples Hosp, Clin Med Coll 2, Obstet & Gynecol, Shenzhen, Peoples R China
2.Jilin Univ, Coll Vet Med, Key Lab Zoonosis, Minist Educ, Changchun, Peoples R China
3.Tsinghua Univ, Sch Life Sci, Beijing, Peoples R China
4.Jinan Univ, Shenzhen Peoples Hosp, Clin Med Coll 2, Emergency Dept, Shenzhen, Peoples R China
5.Jinan Univ, Shenzhen Peoples Hosp, Clin Med Coll 2, Cytotherapy Lab, Shenzhen, Peoples R China
6.Jinan Univ, Obstet & Gynecol, Shenzhen Baoan Maternal & Child Hlth Hosp, Shenzhen, Peoples R China
7.First Affiliated Hosp Jinan Univ, Obstet & Gynecol, Guangzhou, Peoples R China
8.Southern Univ Sci & Technol, Affiliated Hosp 2, Biotherapy Res Ctr, Sch Med, Shenzhen, Peoples R China
9.Shenzhen Third Peoples Hosp, Biotherapy Res Ctr, Natl Clin Res Ctr Infect Dis, Shenzhen, Peoples R China

Gao, Yu,Zhou, Min,Zhang, Wen,et al. NLRP3 mediates trophoblastic inflammasome activation and protects against Listeria monocytogenes infection during pregnancy[J]. Annals of Translational Medicine,2022.

Gao, Yu.,Zhou, Min.,Zhang, Wen.,Jiang, Jinxing.,Ouyang, Zhibin.,...&Li, Nini.(2022).NLRP3 mediates trophoblastic inflammasome activation and protects against Listeria monocytogenes infection during pregnancy.Annals of Translational Medicine.

Gao, Yu,et al."NLRP3 mediates trophoblastic inflammasome activation and protects against Listeria monocytogenes infection during pregnancy".Annals of Translational Medicine (2022).