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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Cell. Infect. Microbiol. | doi: 10.3389/fcimb.2018.00287

The key role of c-Fos for immune regulation and bacterial dissemination in Brucella infected macrophage

 Huynh T. Hop1, Lauren Togonon Arayan1,  Tran Xuan Ngoc Huy1,  Alisha Wehdnesday Bernardo Reyes1,  Son Hai Vu1, Wongi Min1, Hu Jang Lee1,  Man Hee Rhee2, Hong Hee Chang1 and  Suk Kim1*
  • 1Gyeongsang National University, South Korea
  • 2Kyungpook National University, South Korea

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.

Keywords: Brucella abortus, c-fos, MAPKs, TLR-4, IL-10

Received: 18 Apr 2018; Accepted: 27 Jul 2018.

Edited by:

Jean-Pierre Gorvel, Centre national de la recherche scientifique (CNRS), France

Reviewed by:

Thomas A. Ficht, Texas A&M University, United States
Anne Keriel, Institut National de la Santé et de la Recherche Médicale (INSERM), France  

Copyright: © 2018 Hop, Arayan, Huy, Reyes, Vu, Min, Lee, Rhee, Chang and Kim. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Prof. Suk Kim, Gyeongsang National University, Jinju, South Korea, kimsuk@gnu.ac.kr