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

2018 
// Dong Zhou 1, 2, * , Fei-Jie Zhi 1, 2, * , Mao-Zhen Qi 1, 2 , Fu-Rong Bai 1, 2 , Guangdong Zhang 1, 2 , Jun-Mei Li 1, 2 , Huan Liu 1, 2 , Hua-Tao Chen 1, 2 , Peng-Fei Lin 1, 2 , Ke-Qiong Tang 1, 2 , Wei Liu 1, 2 , Ya-Ping Jin 1, 2 and Ai-Hua Wang 2 1 Key Laboratory of Animal Biotechnology of The Ministry of Agriculture, Northwest AF goat alveolar macrophages; unfolded protein response; cytokines Received: October 03, 2017      Accepted: December 04, 2017      Published: December 26, 2017 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 (ΔGntR) was constructed. The type IV secretion system (T4SS) virulence factor genes ( VirB2 , VirB6 , and VirB8 ) were down-expression in ΔGntR. ΔGntR could infect and proliferate to high titers in GAMs without a significant difference compared with the parental strain. ΔGntR 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. ΔGntR increased greatly the number of Brucella CFUs in the inactive ER stress state in GAMs. Meanwhile, ΔGntR infection increased the levels of IFN-γ, IL-1β, and TNF-α, indicating ΔGntR 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.
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