Activation of NF-kB-Mediated TNF-Induced Antimicrobial Immunity Is Required for the Efficient Brucella abortus Clearance in RAW 264.7 Cells

In this study, we explore the regulatory roles of pro-inflammatory cytokine tumor necrosis factor alpha (TNF) in the innate immunity of macrophages against B. abortus infection. We show that infection of macrophage with B. abortus induces marked expression and secretion of TNF which subsequently bin...

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Main Authors: Huynh T. Hop, Alisha W. B. Reyes, Tran X. N. Huy, Lauren T. Arayan, WonGi Min, Hu J. Lee, Man H. Rhee, Hong H. Chang, Suk Kim
Format: Article
Language:English
Published: Frontiers Media S.A. 2017-10-01
Series:Frontiers in Cellular and Infection Microbiology
Subjects:
Online Access:http://journal.frontiersin.org/article/10.3389/fcimb.2017.00437/full
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author Huynh T. Hop
Alisha W. B. Reyes
Tran X. N. Huy
Lauren T. Arayan
WonGi Min
Hu J. Lee
Man H. Rhee
Hong H. Chang
Suk Kim
Suk Kim
author_facet Huynh T. Hop
Alisha W. B. Reyes
Tran X. N. Huy
Lauren T. Arayan
WonGi Min
Hu J. Lee
Man H. Rhee
Hong H. Chang
Suk Kim
Suk Kim
author_sort Huynh T. Hop
collection DOAJ
description In this study, we explore the regulatory roles of pro-inflammatory cytokine tumor necrosis factor alpha (TNF) in the innate immunity of macrophages against B. abortus infection. We show that infection of macrophage with B. abortus induces marked expression and secretion of TNF which subsequently binds to TNF receptor 1 (TNFR-1) and activates a downstream signaling cascade of the innate immunity. Blocking of TNF signaling resulted in a notable increase of B. abortus survival which was associated with an increase of anti-inflammatory cytokine interleukin 10 (IL-10), a beneficial effector of Brucella survival, as well as remarkable decrease of reactive oxygen species (ROS) and nitric oxide (NO), antibrucella molecules. However, surprisingly, the interference of TNF did not show any influence on phagolysosome and cell death events. Furthermore, the transcriptional factor NF-kB was found to be a main mediator of TNF signaling when blocking of NF-kB pathway drastically suppressed the TNF-induced brucellacidal effect. Taken together, these findings clearly indicate that the immune cascade activated by TNF/TNFR-1 is required for the sufficient resistance to B. abortus survival in macrophages.
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spelling doaj.art-749e76a5d019471aa774b57cabe50aa02022-12-21T19:48:18ZengFrontiers Media S.A.Frontiers in Cellular and Infection Microbiology2235-29882017-10-01710.3389/fcimb.2017.00437296342Activation of NF-kB-Mediated TNF-Induced Antimicrobial Immunity Is Required for the Efficient Brucella abortus Clearance in RAW 264.7 CellsHuynh T. Hop0Alisha W. B. Reyes1Tran X. N. Huy2Lauren T. Arayan3WonGi Min4Hu J. Lee5Man H. Rhee6Hong H. Chang7Suk Kim8Suk Kim9Institute of Animal Medicine, College of Veterinary Medicine, Gyeongsang National University, Jinju, South KoreaInstitute of Animal Medicine, College of Veterinary Medicine, Gyeongsang National University, Jinju, South KoreaInstitute of Animal Medicine, College of Veterinary Medicine, Gyeongsang National University, Jinju, South KoreaInstitute of Animal Medicine, College of Veterinary Medicine, Gyeongsang National University, Jinju, South KoreaInstitute of Animal Medicine, College of Veterinary Medicine, Gyeongsang National University, Jinju, South KoreaInstitute of Animal Medicine, College of Veterinary Medicine, Gyeongsang National University, Jinju, South KoreaCollege of Veterinary Medicine, Kyungpook National University, Daegu, South KoreaInstitute of Agriculture and Life Science, Gyeongsang National University, Jinju, South KoreaInstitute of Animal Medicine, College of Veterinary Medicine, Gyeongsang National University, Jinju, South KoreaInstitute of Agriculture and Life Science, Gyeongsang National University, Jinju, South KoreaIn this study, we explore the regulatory roles of pro-inflammatory cytokine tumor necrosis factor alpha (TNF) in the innate immunity of macrophages against B. abortus infection. We show that infection of macrophage with B. abortus induces marked expression and secretion of TNF which subsequently binds to TNF receptor 1 (TNFR-1) and activates a downstream signaling cascade of the innate immunity. Blocking of TNF signaling resulted in a notable increase of B. abortus survival which was associated with an increase of anti-inflammatory cytokine interleukin 10 (IL-10), a beneficial effector of Brucella survival, as well as remarkable decrease of reactive oxygen species (ROS) and nitric oxide (NO), antibrucella molecules. However, surprisingly, the interference of TNF did not show any influence on phagolysosome and cell death events. Furthermore, the transcriptional factor NF-kB was found to be a main mediator of TNF signaling when blocking of NF-kB pathway drastically suppressed the TNF-induced brucellacidal effect. Taken together, these findings clearly indicate that the immune cascade activated by TNF/TNFR-1 is required for the sufficient resistance to B. abortus survival in macrophages.http://journal.frontiersin.org/article/10.3389/fcimb.2017.00437/fullB. abortusTNFTNFR-1ROSNONF-kB transcriptional factor
spellingShingle Huynh T. Hop
Alisha W. B. Reyes
Tran X. N. Huy
Lauren T. Arayan
WonGi Min
Hu J. Lee
Man H. Rhee
Hong H. Chang
Suk Kim
Suk Kim
Activation of NF-kB-Mediated TNF-Induced Antimicrobial Immunity Is Required for the Efficient Brucella abortus Clearance in RAW 264.7 Cells
Frontiers in Cellular and Infection Microbiology
B. abortus
TNF
TNFR-1
ROS
NO
NF-kB transcriptional factor
title Activation of NF-kB-Mediated TNF-Induced Antimicrobial Immunity Is Required for the Efficient Brucella abortus Clearance in RAW 264.7 Cells
title_full Activation of NF-kB-Mediated TNF-Induced Antimicrobial Immunity Is Required for the Efficient Brucella abortus Clearance in RAW 264.7 Cells
title_fullStr Activation of NF-kB-Mediated TNF-Induced Antimicrobial Immunity Is Required for the Efficient Brucella abortus Clearance in RAW 264.7 Cells
title_full_unstemmed Activation of NF-kB-Mediated TNF-Induced Antimicrobial Immunity Is Required for the Efficient Brucella abortus Clearance in RAW 264.7 Cells
title_short Activation of NF-kB-Mediated TNF-Induced Antimicrobial Immunity Is Required for the Efficient Brucella abortus Clearance in RAW 264.7 Cells
title_sort activation of nf kb mediated tnf induced antimicrobial immunity is required for the efficient brucella abortus clearance in raw 264 7 cells
topic B. abortus
TNF
TNFR-1
ROS
NO
NF-kB transcriptional factor
url http://journal.frontiersin.org/article/10.3389/fcimb.2017.00437/full
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