Open AccessHMGB1 release from trophoblasts contributes to inflammation during Brucella melitensis infection
Author(s) -
Liu Xiaofeng,
Zhou Mi,
Wu Jing,
Wang Jun,
Peng Qisheng
Publication year - 2019
Publication title -
cellular microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.542
H-Index - 138
eISSN - 1462-5822
pISSN - 1462-5814
DOI - 10.1111/cmi.13080
Subject(s) - brucella melitensis , hmgb1 , placenta , biology , inflammation , immunology , nicotinamide adenine dinucleotide phosphate , brucella , oxidase test , fetus , pregnancy , brucellosis , enzyme , biochemistry , genetics
Brucella melitensis infection causes acute necrotizing inflammation in pregnant animals; however, the pathophysiological mechanisms leading to placentitis are unknown. Here, we demonstrate that high‐mobility group box 1 (HMGB1) acts as a mediator of placenta inflammation in B . melitensis ‐infected pregnant mice model. HMGB1 levels were increased in trophoblasts or placental explant during B. melitensis infection. Inhibition of HMGB1 activity with neutralising antibody significantly reduced the secretion of inflammatory cytokines in B. melitensis ‐infected trophoblasts or placenta, whereas administration of recombinant HMGB1 (rHMGB1) increased the inflammatory response. Mechanistically, this decreased inflammatory response results from inhibition of HMGB1 activity, which cause the suppression of both mitogen‐activated protein kinases and nuclear factor kappa‐light‐chain‐enhancer of activated B cells (NF‐κB) activation. Moreover, neutralising antibody to HMGB1 prevented B. melitensis infection‐induced activation of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase in trophoblasts. In contrast, in vitro stimulation of trophoblasts with rHMGB1 caused activation of NADPH oxidase and increased the production of ROS, which contributes to high bacterial burden within trophoblasts or placenta. In vivo, treatment with anti‐HMGB1 antibody increases the number of Brucella survival within placenta in B. melitensis ‐infected pregnant mice but successfully reduced the severity of placentitis and abortion.