| DC-derived IL-18 drives Treg differentiation, murine Helicobacter pylori-specific immune tolerance, and asthma protection. | |
| | |
MedLine Citation:
|
PMID: 22307326 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
Persistent colonization with the gastric bacterial pathogen Helicobacter pylori causes gastritis and predisposes infected individuals to gastric cancer. Conversely, it is also linked to protection from allergic, chronic inflammatory, and autoimmune diseases. We demonstrate here that H. pylori inhibits LPS-induced maturation of DCs and reprograms DCs toward a tolerance-promoting phenotype. Our results showed that DCs exposed to H. pylori in vitro or in vivo failed to induce T cell effector functions. Instead, they efficiently induced expression of the forkhead transcription factor FoxP3, the master regulator of Tregs, in naive T cells. Depletion of DCs in mice infected with H. pylori during the neonatal period was sufficient to break H. pylori-specific tolerance. DC depletion resulted in improved control of the infection but also aggravated T cell-driven immunopathology. Consistent with the mouse data, DCs infiltrating the gastric mucosa of human H. pylori carriers exhibited a semimature DC-SIGN(+)HLA-DR(hi)CD80(lo)CD86(lo) phenotype. Mechanistically, the tolerogenic activity of H. pylori-experienced DCs was shown to require IL-18 in vitro and in vivo; DC-derived IL-18 acted directly on T cells to drive their conversion to Tregs. CD4(+)CD25(+) Tregs from infected wild-type mice but not Il18(-/-) or Il18r1(-/-) mice prevented airway inflammation and hyperresponsiveness in an experimental model of asthma. Taken together, our results indicate that tolerogenic reprogramming of DCs ensures the persistence of H. pylori and protects against allergic asthma in a process that requires IL-18. |
| | |
Authors:
|
Mathias Oertli; Malin Sundquist; Iris Hitzler; Daniela B Engler; Isabelle C Arnold; Sebastian Reuter; Joachim Maxeiner; Malin Hansson; Christian Taube; Marianne Quiding-Järbrink; Anne Müller |
Related Documents
:
|
22795876 - Human tissues contain cd141hi cross-presenting dendritic cells with functional homology... 18782266 - Beginning of the end of (understanding) the immune response. 22855296 - Managing macrophages in rheumatoid arthritis by reform or removal. 21178006 - P-rex1 and vav1 cooperate in the regulation of formyl-methionyl-leucyl-phenylalanine-de... 23486586 - Histophysiology of immune system and barrier organs in the late period of orchiectomy i... 21480956 - Expression of heat shock proteins in classical hodgkin lymphoma: correlation with apopt... |
Publication Detail:
|
Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2012-02-06 |
Journal Detail:
|
Title: The Journal of clinical investigation Volume: 122 ISSN: 1558-8238 ISO Abbreviation: J. Clin. Invest. Publication Date: 2012 Mar |
Date Detail:
|
Created Date: 2012-03-01 Completed Date: 2012-04-30 Revised Date: 2013-05-20 |
Medline Journal Info:
|
Nlm Unique ID: 7802877 Medline TA: J Clin Invest Country: United States |
Other Details:
|
Languages: eng Pagination: 1082-96 Citation Subset: AIM; IM |
Affiliation:
|
Institute of Molecular Cancer Research, University of Zürich, Zürich, Switzerland. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Adult Animals Asthma / prevention & control* CD4-Positive T-Lymphocytes / microbiology Cell Differentiation Coculture Techniques Female Gastric Mucosa / microbiology Helicobacter Infections / microbiology Helicobacter pylori / metabolism* Humans Immune Tolerance Interleukin-18 / metabolism* Interleukin-2 Receptor alpha Subunit / biosynthesis Ligands Lipopolysaccharides / metabolism Male Mice Middle Aged Phenotype T-Lymphocytes, Regulatory / cytology* |
| Chemical | |
Reg. No./Substance:
|
0/Interleukin-18; 0/Interleukin-2 Receptor alpha Subunit; 0/Ligands; 0/Lipopolysaccharides |
| Comments/Corrections | |
Comment In:
|
J Clin Invest. 2012 Mar 1;122(3):801-4
[PMID:
22307323
]
|
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: ChIP sequencing of cyclin D1 reveals a transcriptional role in chromosomal instability in mice.
Next Document: Anti-ganglioside antibody internalization attenuates motor nerve terminal injury in a mouse model of...