The Key Role of c-Fos for Immune Regulation and Bacterial Dissemination in Brucella Infected Macrophage

被引:48
作者
Hop, Huynh T. [1 ]
Arayan, Lauren T. [1 ]
Huy, Tran X. N. [1 ]
Reyes, Alisha W. B. [1 ]
Vu, Son H. [1 ]
Min, Wongi [1 ]
Lee, Hu J. [1 ]
Rhee, Man H. [2 ]
Chang, Hong H. [3 ]
Kim, Suk [1 ,3 ]
机构
[1] Gyeongsang Natl Univ, Inst Anim Med, Coll Vet Med, Jinju, South Korea
[2] Kyungpook Natl Univ, Coll Vet Med, Daegu, South Korea
[3] Gyeongsang Natl Univ, Inst Agr & Life Sci, Jinju, South Korea
关键词
Brucella abortus; c-Fos; MAPKs; TLR-4; IL-10; MYCOBACTERIUM-TUBERCULOSIS; INTRACELLULAR REPLICATION; INFLAMMATORY RESPONSE; CELL-PROLIFERATION; FLOW-CYTOMETRY; ABORTUS; EXPRESSION; APOPTOSIS; DEATH; MICE;
D O I
10.3389/fcimb.2018.00287
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
The cellular oncogene c-Fos (c-Fos) is a component of activator protein 1 (AP1), a master transcriptional regulator of cells. The suppression of c-Fos signaling by siRNA treatment resulted in significant induction of TLR4, which subsequently activates p38 and ERK1/2 mitogen-activated protein kinases (MAPKs) and enhances F-actin polymerization, leading to an increase in B. abortus phagocytosis. During B. abortus infection, c-Fos signaling is induced, which activates the downstream innate-immunity signaling cascade for bacterial clearance. The inhibition of c-Fos signaling led to increased production of interleukin 10 (IL-10), which partially suppressed lysosome-mediated killing, resulting in increased survival of B. abortus inside macrophages. We present evidence of the regulatory role played by the c-Fos pathway in proliferation during B. abortus infection; however, this was independent of the anti-Brucella effect of this pathway. Another finding is the essential contribution of c-Fos/TRAIL to infected-cell necrosis, which is a key event in bacterial dissemination. These data provide the mechanism via which c-Fos participates in host defense mechanisms against Brucella infection and in bacterial dissemination by macrophages.
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页数:16
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