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Review
. 2022 Nov 2;23(21):13417.
doi: 10.3390/ijms232113417.

Inflammatory Mechanism of Brucella Infection in Placental Trophoblast Cells

Yu Xiao  1 , Mengjuan Li  1 , Xiaoyi Guo  1 , Hui Zeng  1 , Xuehong Shuai  1 , Jianhua Guo  1 , Qingzhou Huang  1 , Yuefeng Chu  2 , Bo Zhou  3 , Jake Wen  4 , Jun Liu  3 , Hanwei Jiao  1   5
Affiliations
Review

Inflammatory Mechanism of Brucella Infection in Placental Trophoblast Cells

Yu Xiao et al. Int J Mol Sci. .

Abstract

Brucellosis is a severe zoonotic infectious disease caused by the infection of the Brucella, which is widespread and causes considerable economic losses in underdeveloped areas. Brucella is a facultative intracellular bacteria whose main target cells for infection are macrophages, placental trophoblast cells and dendritic cells. The main clinical signs of Brucella infection in livestock are reproductive disorders and abortion. At present, the pathogenesis of placentitis or abortion caused by Brucella in livestock is not fully understood, and further research on the effect of Brucella on placental development is still necessary. This review will mainly introduce the research progress of Brucella infection of placental trophoblast cells as well as the inflammatory response caused by it, explaining the molecular regulation mechanism of Brucella leading to reproductive system disorders and abortion, and also to provide the scientific basis for revealing the pathogenesis and infection mechanism of Brucella.

Keywords: Brucella; infection mechanism; inflammatory response; pathogenesis; trophoblast.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Intracellular process of Brucella invading CTB. Green arrows indicate the infection pathway of Brucella; red arrows indicate adsorption, acquisition or capture; gray arrows indicate co-cause and mediation; orange arrows indicate interactions; blue arrows indicate binding; black arrows indicate loss.
Figure 2
Figure 2
VceC mediates IREα inflammatory responses and apoptosis in cells. ①②: VceC ectopic to rough ER through Brucella T4SS. RER is stimulated by VceC and causes ER stress to increase unfolded products, and prolonged stress leads to UPR, activation of ATF6, PERK and IREα metabolic pathways. ③④: VceC binds to the GRP78 chaperone at the ER to induce the IREα inflammatory pathway. ⑤–⑨: IREα is activated and recruits TRAF2 to the ER membrane and triggers NOD1/2 homo-oligomerization and activation. TRAF2 binds and k63-polyubiquitinates RIP2, both of which are involved in NOD1/2 signaling to mediate the collection of TAK1, ultimately activating NF-κB, thus increasing the levels of inflammatory factors such as IL-6, IL-12p40, and causing the placental occurrence of inflammation. ⑩–⑫: VceC binding to GRP78 affecting the changes of the PERK pathway in host cells is still controversial. ER stress induces another important pathway, the PERK apoptosis pathway, which induces the expression of CHOP by gene Ddit3, which eventually leads to apoptosis.
Figure 3
Figure 3
The interaction between Brucella and phagocytic cells after infection of trophoblast cells. After the trophoblast cells are attacked by Brucella, they begin to produce HMGB1 and excrete HMGB1, increasing the concentration of ROS in response to changes in the intracellular environment and secrete cytokines such as IL-6, IL-8, RANTES and TNF-α. Monocytes and neutrophils move to the placental infection site and secrete a large number of inflammatory factors after receiving the stimulation of Brucella and cytokines, causing placental inflammatory infiltration.“++++” indicates an increase in the degree of inflammatory response, which is a positive feedback of inflammatory cells to trophoblast cell signals. The specific inflammatory secreted factors are shown in Table 1.
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References

    1. Zhang H., Dou X., Li Z., Zhang Y., Zhang J., Guo F., Wang Y., Wang Z., Li T., Gu X., et al. Expression and regulation of the ery operon of Brucella melitensis in human trophoblast cells. Exp. Ther. Med. 2016;12:2723–2728. doi: 10.3892/etm.2016.3688. - DOI - PMC - PubMed
    1. Shi B., Li X., Li B., Zheng N.X., Li M., Liu Y., Li C.H., Yan F., He W., Zhao L.Y., et al. Construction and evaluation of the Brucella double gene knock-out vaccine strain MB6 Δbp26ΔwboA (RM6) Zoonoses. 2022;2:29. doi: 10.15212/ZOONOSES-2022-0031. - DOI
    1. Yu J., Li S., Wang L., Dong Z., Si L., Bao L., Wu L. Pathogenesis of Brucella epididymoorchitis-game of Brucella death. Crit Rev. Microbiol. 2022;48:96–120. doi: 10.1080/1040841X.2021.1944055. - DOI - PubMed
    1. Almiron M.A., Roset M.S., Sanjuan N. The Aggregation of Brucella abortus Occurs Under Microaerobic Conditions and Promotes Desiccation Tolerance and Biofilm Formation. Open Microbiol. J. 2013;7:87–91. doi: 10.2174/1874285801307010087. - DOI - PMC - PubMed
    1. Erkyihun G.A., Gari F.R., Kassa G.M. Bovine brucellosis and its public health significance in Ethiopia. Zoonoses. 2022;2:15. doi: 10.15212/ZOONOSES-2022-0005. - DOI
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