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Brucella induces unfolded protein response and inflammatory response via GntR in alveolar macrophages.


ABSTRACT: Brucella is an intracellular bacterium that causes the zoonosis brucellosis worldwide. Alveolar macrophages (AM) constitute the main cell target of inhaled Brucella. Brucella thwarts immune surveillance and evokes endoplasmic reticulum (ER) stress to replicate in macrophages via virulence factors. The GntR regulators family was concentrated as an important virulence factor in controlling virulence and intracellular survival of Brucella. However, the detailed underlying mechanism for the host-pathogen interaction is poorly understood. In this study the BSS2_II0438 mutant (?GntR) was constructed. The type IV secretion system (T4SS) virulence factor genes (VirB2, VirB6, and VirB8) were down-expression in ?GntR. ?GntR could infect and proliferate to high titers in GAMs without a significant difference compared with the parental strain. ?GntR infection increased the expression of ER stress marker genes GRP78, ATF6, and PERK in the early stages of its intracellular cycle but decreased the expression of these genes in the late stages. ?GntR increased greatly the number of Brucella CFUs in the inactive ER stress state in GAMs. Meanwhile, ?GntR infection increased the levels of IFN-?, IL-1?, and TNF-?, indicating ?GntR could induce the secretion of inflammatory but not anti-inflammatory cytokines IL-10. Taken together, our results clarified the role of the GntR in B. suis. S2 virulence expression and elucidated that GntR is potentially involved in the signaling pathway of the Brucella-induced UPR and inflammatory response in GAMs.

SUBMITTER: Zhou D 

PROVIDER: S-EPMC5797042 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature

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<i>Brucella</i> induces unfolded protein response and inflammatory response via GntR in alveolar macrophages.

Zhou Dong D   Zhi Fei-Jie FJ   Qi Mao-Zhen MZ   Bai Fu-Rong FR   Zhang Guangdong G   Li Jun-Mei JM   Liu Huan H   Chen Hua-Tao HT   Lin Peng-Fei PF   Tang Ke-Qiong KQ   Liu Wei W   Jin Ya-Ping YP   Wang Ai-Hua AH  

Oncotarget 20171226 4


<i>Brucella</i> is an intracellular bacterium that causes the zoonosis brucellosis worldwide. Alveolar macrophages (AM) constitute the main cell target of inhaled <i>Brucella</i>. <i>Brucella</i> thwarts immune surveillance and evokes endoplasmic reticulum (ER) stress to replicate in macrophages via virulence factors. The GntR regulators family was concentrated as an important virulence factor in controlling virulence and intracellular survival of <i>Brucella</i>. However, the detailed underlyin  ...[more]

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