Article ; Online: Suppression of innate immune pathology by regulatory T cells during Influenza A virus infection of immunodeficient mice.
2010 Volume 84, Issue 24, Page(s) 12564–12575
Abstract: ... Treg) cells in limiting pathology induced by influenza A virus (IAV) infection. Using lymphocyte-deficient ... these results suggested that innate immune pathology and virus-induced pathology are the two main contributors ... ameliorating effect was mediated through the suppression of innate immune pathology. Mechanistically ...
| Abstract | 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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| MeSH term(s) | Animals ; Antibodies, Neutralizing/pharmacology ; B-Lymphocytes/immunology ; B-Lymphocytes/virology ; Biomarkers, Tumor/genetics ; Biomarkers, Tumor/metabolism ; 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 ; Lung Diseases/prevention & control ; Lung Diseases/virology ; Lymphocyte Depletion ; Macrophages/immunology ; Macrophages/virology ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Mice, Knockout ; Mice, Nude ; Monocytes/immunology ; Monocytes/virology ; Oligonucleotide Array Sequence Analysis ; Orthomyxoviridae Infections/immunology ; Orthomyxoviridae Infections/pathology ; Orthomyxoviridae Infections/virology ; RNA, Messenger/genetics ; Reverse Transcriptase Polymerase Chain Reaction ; T-Lymphocytes/immunology ; T-Lymphocytes/virology ; T-Lymphocytes, Regulatory/immunology ; T-Lymphocytes, Regulatory/virology ; Virus Replication/immunology | |||||
| Chemical Substances | Antibodies, Neutralizing ; Biomarkers, Tumor ; Chemokine CCL8 ; Chemokines ; Cytokines ; Homeodomain Proteins ; RNA, Messenger ; RAG-1 protein (128559-51-3) | |||||
| Keywords | covid19 | |||||
| Language | English | |||||
| Publishing date | 2010-10-13 | |||||
| Publishing country | United States | |||||
| Document type | Journal Article ; Research Support, Non-U.S. Gov't | |||||
| ZDB-ID | 80174-4 | |||||
| ISSN | 1098-5514 ; 0022-538X | |||||
| ISSN (online) | 1098-5514 | |||||
| ISSN | 0022-538X | |||||
| DOI | 10.1128/JVI.01559-10 | |||||
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| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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