| CCR2 plays a critical role in dendritic cell maturation: possible role of CCL2 and NF-kappa B. | |
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MedLine Citation:
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PMID: 20404272 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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We postulated that CCR2-driven activation of the transcription factor NF-kappaB plays a critical role in dendritic cell (DC) maturation (e.g., migration, costimulation, and IL-12p70 production), necessary for the generation of protective immune responses against the intracellular pathogen Leishmania major. Supporting this notion, we found that CCR2, its ligand CCL2, and NF-kappaB were required for CCL19 production and adequate Langerhans cell (LC) migration both ex vivo and in vivo. Furthermore, a role for CCR2 in upregulating costimulatory molecules was indicated by the reduced expression of CD80, CD86, and CD40 in Ccr2(-/-) bone marrow-derived dendritic cells (BMDCs) compared with wild-type (WT) BMDCs. Four lines of evidence suggested that CCR2 plays a critical role in the induction of protective immunity against L. major by regulating IL-12p70 production and migration of DC populations such as LCs. First, compared with WT, Ccr2(-/-) lymph node cells, splenocytes, BMDCs, and LCs produced lower levels of IL-12p70 following stimulation with LPS/IFN-gamma or L. major. Second, a reduced number of LCs carried L. major from the skin to the draining lymph nodes in Ccr2(-/-) mice compared with WT mice. Third, early treatment with exogenous IL-12 reversed the susceptibility to L. major infection in Ccr2(-/-) mice. Finally, disruption of IL-12p70 in radioresistant cells, such as LCs, but not in BMDCs resulted in the inability to mount a fully protective immune response in bone marrow chimeric mice. Collectively, our data point to an important role for CCR2-driven activation of NF-kappaB in the regulation of DC/LC maturation processes that regulate protective immunity against intracellular pathogens. |
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Authors:
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Fabio Jimenez; Marlon P Quinones; Hernan G Martinez; Carlos A Estrada; Kassandra Clark; Edgar Garavito; Jessica Ibarra; Peter C Melby; Seema S Ahuja |
Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, Non-P.H.S. Date: 2010-04-19 |
Journal Detail:
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Title: Journal of immunology (Baltimore, Md. : 1950) Volume: 184 ISSN: 1550-6606 ISO Abbreviation: J. Immunol. Publication Date: 2010 May |
Date Detail:
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Created Date: 2010-05-20 Completed Date: 2010-07-19 Revised Date: 2011-09-26 |
Medline Journal Info:
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Nlm Unique ID: 2985117R Medline TA: J Immunol Country: United States |
Other Details:
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Languages: eng Pagination: 5571-81 Citation Subset: AIM; IM |
Affiliation:
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Audie L. Murphy Division, Veterans Administration Center for Research on AIDS and HIV-1 Infection, South Texas Veterans Health Care System, San Antonio, TX 78229, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Cell Differentiation / genetics, immunology* Cell Movement / genetics, immunology Cells, Cultured Chemokine CCL2 / deficiency, genetics, physiology* Dendritic Cells / immunology*, metabolism*, pathology Interleukin-12 / biosynthesis, genetics Langerhans Cells / immunology, metabolism, pathology Leishmania major / immunology Leishmaniasis, Cutaneous / immunology, metabolism, pathology Mice Mice, Inbred C57BL Mice, Knockout Mice, SCID Models, Immunological NF-kappa B / metabolism, physiology* Receptors, CCR2 / biosynthesis, deficiency, physiology* Transcriptional Activation / immunology Up-Regulation / genetics, immunology |
| Grant Support | |
ID/Acronym/Agency:
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R01 AI048644-01A1/AI/NIAID NIH HHS; R01 AR052755-01A2/AR/NIAMS NIH HHS; R01-AI48644/AI/NIAID NIH HHS; R01-AR052755/AR/NIAMS NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Ccl2 protein, mouse; 0/Ccr2 protein, mouse; 0/Chemokine CCL2; 0/NF-kappa B; 0/Receptors, CCR2; 187348-17-0/Interleukin-12 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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