PMID- 24293633
OWN - NLM
STAT- MEDLINE
DCOM- 20140227
LR  - 20220409
IS  - 1550-6606 (Electronic)
IS  - 0022-1767 (Linking)
VI  - 192
IP  - 1
DP  - 2014 Jan 1
TI  - Helicobacter pylori cytotoxin-associated gene A impairs human dendritic cell 
      maturation and function through IL-10-mediated activation of STAT3.
PG  - 316-23
LID - 10.4049/jimmunol.1302476 [doi]
AB  - Helicobacter pylori infection induces chronic gastric inflammation that can 
      progress to cancer. In this process, the virulence factor cytotoxin-associated 
      gene A (CagA) plays a central role by directly altering epithelial cell signaling 
      and inducing a strong Th1 immune response, which contributes to carcinogenesis. 
      It is still barely understood how the bacterium evades clearance despite this 
      solid immune response and persists lifelong. Dendritic cells (DCs) play a major 
      role in determining the adaptive immune response toward H. pylori, and high 
      levels of regulatory T cells have been detected infiltrating the gastric mucosa 
      of H. pylori-infected patients, which contribute to bacterial persistence. 
      Although murine studies indicate that H. pylori induces tolerization of DCs and 
      impairs DC maturation, the virulence determinants involved are still 
      controversial. Moreover, the signaling cascades engaged in human DC tolerization 
      upon H. pylori infection remain unknown. In the current study, we analyzed the 
      effect of H. pylori infection on human DC maturation and function, focusing on 
      the virulence factors implicated and signaling pathways involved. Our results 
      reveal that CagA is crucial for DC tolerization by modulating IL-10 secretion 
      and, in turn, STAT3 phosphorylation, favoring a regulatory T cell immune 
      response. Our findings help to unravel the paradox why CagA-positive strains, 
      although eliciting a stronger inflammatory response, have overcome evolutionary 
      pressure and persisted in their human host.
FAU - Kaebisch, Romy
AU  - Kaebisch R
AD  - Institut fur Medizinische Mikrobiologie, Immunologie und Hygiene, Technische 
      Universitat Munchen, 81675 Munich, Germany;
FAU - Mejias-Luque, Raquel
AU  - Mejias-Luque R
FAU - Prinz, Christian
AU  - Prinz C
FAU - Gerhard, Markus
AU  - Gerhard M
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20131129
PL  - United States
TA  - J Immunol
JT  - Journal of immunology (Baltimore, Md. : 1950)
JID - 2985117R
RN  - 0 (Antigens, Bacterial)
RN  - 0 (Bacterial Proteins)
RN  - 0 (Cytokines)
RN  - 0 (STAT3 Transcription Factor)
RN  - 0 (cagA protein, Helicobacter pylori)
RN  - 130068-27-8 (Interleukin-10)
SB  - IM
MH  - Antigens, Bacterial/*genetics/metabolism
MH  - Bacterial Proteins/*genetics/metabolism
MH  - Cells, Cultured
MH  - Cytokines/biosynthesis
MH  - Dendritic Cells/*immunology/*metabolism
MH  - Helicobacter pylori/*genetics
MH  - Humans
MH  - Interleukin-10/*metabolism
MH  - STAT3 Transcription Factor/*metabolism
MH  - Signal Transduction
MH  - T-Lymphocytes, Regulatory/immunology/metabolism
EDAT- 2013/12/03 06:00
MHDA- 2014/02/28 06:00
CRDT- 2013/12/03 06:00
PHST- 2013/12/03 06:00 [entrez]
PHST- 2013/12/03 06:00 [pubmed]
PHST- 2014/02/28 06:00 [medline]
AID - jimmunol.1302476 [pii]
AID - 10.4049/jimmunol.1302476 [doi]
PST - ppublish
SO  - J Immunol. 2014 Jan 1;192(1):316-23. doi: 10.4049/jimmunol.1302476. Epub 2013 Nov 
      29.