| Suppression of innate immune pathology by regulatory T cells during Influenza A virus infection of immunodeficient mice. | |
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MedLine Citation:
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PMID: 20943986 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The viral infection of higher vertebrates elicits potent innate and adaptive host immunity. However, an excessive or inappropriate immune response also may lead to host pathology that often is more severe than the direct effects of viral replication. Therefore, several mechanisms exist that regulate the magnitude and class of the immune response. Here, we have examined the potential involvement of regulatory T (Treg) cells in limiting pathology induced by influenza A virus (IAV) infection. Using lymphocyte-deficient mice as hosts, we showed that Treg cell reconstitution resulted in a significant delay in weight loss and prolonged survival following infection. The adoptively transferred Treg cells did not affect the high rate of IAV replication in the lungs of lymphocyte-deficient hosts, and therefore their disease-ameliorating effect was mediated through the suppression of innate immune pathology. Mechanistically, Treg cells reduced the accumulation and altered the distribution of monocytes/macrophages in the lungs of IAV-infected hosts. This reduction in lung monocytosis was associated with a specific delay in monocyte chemotactic protein-2 (MCP-2) induction in the infected lungs. Nevertheless, Treg cells failed to prevent the eventual development of severe disease in lymphocyte-deficient hosts, which likely was caused by the ongoing IAV replication. Indeed, using T-cell-deficient mice, which mounted a T-cell-independent B cell response to IAV, we further showed that the combination of virus-neutralizing antibodies and transferred Treg cells led to the complete prevention of clinical disease following IAV infection. Taken together, these results suggested that innate immune pathology and virus-induced pathology are the two main contributors to pathogenesis during IAV infection. |
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Authors:
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Inês Antunes; George Kassiotis |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-10-13 |
Journal Detail:
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Title: Journal of virology Volume: 84 ISSN: 1098-5514 ISO Abbreviation: J. Virol. Publication Date: 2010 Dec |
Date Detail:
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Created Date: 2010-11-24 Completed Date: 2011-01-06 Revised Date: 2011-07-28 |
Medline Journal Info:
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Nlm Unique ID: 0113724 Medline TA: J Virol Country: United States |
Other Details:
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Languages: eng Pagination: 12564-75 Citation Subset: IM |
Affiliation:
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Division of Immunoregulation, MRC National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA, United Kingdom. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Antibodies, Neutralizing / pharmacology B-Lymphocytes / immunology, virology Blotting, Western Chemokine CCL8 / metabolism Chemokines / blood Cytokines / blood Gene Expression Profiling Homeodomain Proteins / physiology Humans Immunity, Innate* Immunoenzyme Techniques Influenza A virus / immunology* Lung Diseases / immunology, prevention & control*, virology Lymphocyte Depletion Macrophages / immunology, virology Mice Mice, Inbred BALB C Mice, Inbred C57BL Mice, Knockout Mice, Nude Monocytes / immunology, virology Oligonucleotide Array Sequence Analysis Orthomyxoviridae Infections / immunology*, pathology, virology RNA, Messenger / genetics Reverse Transcriptase Polymerase Chain Reaction T-Lymphocytes / immunology, virology T-Lymphocytes, Regulatory / immunology*, virology Tumor Markers, Biological / genetics, metabolism Virus Replication / immunology* |
| Grant Support | |
ID/Acronym/Agency:
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U117581330//Medical Research Council |
| Chemical | |
Reg. No./Substance:
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0/Antibodies, Neutralizing; 0/Chemokine CCL8; 0/Chemokines; 0/Cytokines; 0/Homeodomain Proteins; 0/RNA, Messenger; 0/Tumor Markers, Biological; 128559-51-3/RAG-1 protein |
| Comments/Corrections | |
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