PMID- 31249571
OWN - NLM
STAT- MEDLINE
DCOM- 20201020
LR  - 20201020
IS  - 1664-3224 (Electronic)
IS  - 1664-3224 (Linking)
VI  - 10
DP  - 2019
TI  - Fusobacterium nucleatum Aggravates the Progression of Colitis by Regulating M1 
      Macrophage Polarization via AKT2 Pathway.
PG  - 1324
LID - 10.3389/fimmu.2019.01324 [doi]
LID - 1324
AB  - Disordered intestinal flora and discordant immune response are associated with 
      the development of ulcerative colitis (UC). Recent work has described the ability 
      of macrophages to undergo repolarization toward a proinflammatory M1 or 
      anti-inflammatory M2 phenotype in response to particular bacterium-derived 
      signals. Fusobacterium nucleatum (F. nucleatum, Fn) is a species of intestinal 
      commensal bacteria with potential pathogenicity, but its association with UC and 
      how it may contribute to progression of UC is largely unknown. In this study, we 
      provide new evidence that F. nucleatum accumulated heavily in the intestine of UC 
      patients and was accompanied by the secretion of IFN-gamma and the skewing of M1 
      macrophages. Mechanistically, our data showed that F. nucleatum aggravated 
      dextran sodium sulfate (DSS)-induced colitis in the production of Th1-related 
      cytokines IFN-gamma through the AKT2 signaling pathway in vitro and in vivo. To 
      further confirm the disease-relevance of these shifts in macrophage 
      repolarization in response to F. nucleatum, stimulated bone marrow-derived 
      macrophages (BMDMs) were transferred into recipient mice with DSS colitis. This 
      transfer resulted in increased disease activity and inflammatory cytokine 
      production. Taken together, we show clearly that F. nucleatum can promote the 
      progression of UC via proinflammatory M1 macrophage skewing, and targeting F. 
      nucleatum or AKT2 signaling may be a viable means of blocking development of UC.
FAU - Liu, Le
AU  - Liu L
AD  - Guangdong Provincial Key Laboratory of Gastroenterology, State Key Laboratory of 
      Organ Failure Research, Department of Gastroenterology, Nanfang Hospital, 
      Southern Medical University, Guangzhou, China.
FAU - Liang, Liping
AU  - Liang L
AD  - Guangdong Provincial Key Laboratory of Gastroenterology, State Key Laboratory of 
      Organ Failure Research, Department of Gastroenterology, Nanfang Hospital, 
      Southern Medical University, Guangzhou, China.
FAU - Liang, Huifen
AU  - Liang H
AD  - Guangdong Provincial Key Laboratory of Gastroenterology, State Key Laboratory of 
      Organ Failure Research, Department of Gastroenterology, Nanfang Hospital, 
      Southern Medical University, Guangzhou, China.
FAU - Wang, Mingming
AU  - Wang M
AD  - Guangdong Provincial Key Laboratory of Gastroenterology, State Key Laboratory of 
      Organ Failure Research, Department of Gastroenterology, Nanfang Hospital, 
      Southern Medical University, Guangzhou, China.
FAU - Lu, Bingyun
AU  - Lu B
AD  - Guangdong Provincial Key Laboratory of Gastroenterology, State Key Laboratory of 
      Organ Failure Research, Department of Gastroenterology, Nanfang Hospital, 
      Southern Medical University, Guangzhou, China.
FAU - Xue, Meng
AU  - Xue M
AD  - Guangdong Provincial Key Laboratory of Gastroenterology, State Key Laboratory of 
      Organ Failure Research, Department of Gastroenterology, Nanfang Hospital, 
      Southern Medical University, Guangzhou, China.
FAU - Deng, Jun
AU  - Deng J
AD  - Guangdong Provincial Key Laboratory of Gastroenterology, State Key Laboratory of 
      Organ Failure Research, Department of Gastroenterology, Nanfang Hospital, 
      Southern Medical University, Guangzhou, China.
FAU - Chen, Ye
AU  - Chen Y
AD  - Guangdong Provincial Key Laboratory of Gastroenterology, State Key Laboratory of 
      Organ Failure Research, Department of Gastroenterology, Nanfang Hospital, 
      Southern Medical University, Guangzhou, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20190612
PL  - Switzerland
TA  - Front Immunol
JT  - Frontiers in immunology
JID - 101560960
RN  - 82115-62-6 (Interferon-gamma)
RN  - 9042-14-2 (Dextran Sulfate)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
SB  - IM
MH  - Animals
MH  - Cell Differentiation
MH  - Cells, Cultured
MH  - Colitis, Ulcerative/*immunology/microbiology
MH  - Dextran Sulfate
MH  - Disease Models, Animal
MH  - Disease Progression
MH  - Fusobacterium nucleatum/*physiology
MH  - Gastrointestinal Microbiome/*physiology
MH  - Humans
MH  - Interferon-gamma/metabolism
MH  - Macrophage Activation
MH  - Macrophages/*immunology
MH  - Mice
MH  - Proto-Oncogene Proteins c-akt/*metabolism
MH  - Signal Transduction
MH  - Th1 Cells/*immunology
MH  - Th1-Th2 Balance
PMC - PMC6582778
OTO - NOTNLM
OT  - Fusobacterium nucleatum
OT  - M1 macrophage
OT  - gut microbiota
OT  - mucosal barrier
OT  - ulcerative colitis
EDAT- 2019/06/30 06:00
MHDA- 2020/10/21 06:00
PMCR- 2019/01/01
CRDT- 2019/06/29 06:00
PHST- 2019/01/29 00:00 [received]
PHST- 2019/05/24 00:00 [accepted]
PHST- 2019/06/29 06:00 [entrez]
PHST- 2019/06/30 06:00 [pubmed]
PHST- 2020/10/21 06:00 [medline]
PHST- 2019/01/01 00:00 [pmc-release]
AID - 10.3389/fimmu.2019.01324 [doi]
PST - epublish
SO  - Front Immunol. 2019 Jun 12;10:1324. doi: 10.3389/fimmu.2019.01324. eCollection 
      2019.