AUTHOR=Hop Huynh T. , Arayan Lauren T. , Huy Tran X. N. , Reyes Alisha W. B. , Vu Son H. , Min WonGi , Lee Hu J. , Rhee Man H. , Chang Hong H. , Kim Suk 

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

JOURNAL=Frontiers in Cellular and Infection Microbiology

VOLUME=8

YEAR=2018

URL=https://www.frontiersin.org/journals/cellular-and-infection-microbiology/articles/10.3389/fcimb.2018.00287

DOI=10.3389/fcimb.2018.00287

ISSN=2235-2988

ABSTRACT=<p>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 <italic>B. abortus</italic> phagocytosis. During <italic>B. abortus</italic> 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 <italic>B. abortus</italic> inside macrophages. We present evidence of the regulatory role played by the c-Fos pathway in proliferation during <italic>B. abortus</italic> infection; however, this was independent of the anti-<italic>Brucella</italic> 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 <italic>Brucella</italic> infection and in bacterial dissemination by macrophages.</p>