Article ; Online: FimH, a TLR4 ligand, induces innate antiviral responses in the lung leading to protection against lethal influenza infection in mice.
2011 Volume 92, Issue 2, Page(s) 346–355
Abstract: Fimbriae H protein (FimH) is a novel TLR4 ligand that has been shown to stimulate the innate ... the protective role of local delivery of FimH against influenza A infection in a mouse model. We show ... pulmonary pathology following infection in wild type mice compared to TLR4(-/-) mice. Local delivery of FimH ...
| Abstract | Fimbriae H protein (FimH) is a novel TLR4 ligand that has been shown to stimulate the innate immune system and elicits protective responses against bacterial and viral infections. Here, we evaluated the protective role of local delivery of FimH against influenza A infection in a mouse model. We show that intranasal delivery of FimH prior to lethal challenge with influenza A virus, resulted in decreased morbidity and mortality in wild-type, but not TLR4(-/-), mice. Importantly, FimH was able to reduce the early viral burden in the lung leading to minimal cell infiltration into the airway lumen and reduced pulmonary pathology following infection in wild type mice compared to TLR4(-/-) mice. Local delivery of FimH to C57BL/6, not TLR4(-/-), mice in a prophylactic manner increased the IL-12 and RANTES responses as well as neutrophil recruitment into the airway lumen. These effects correlate to the course of influenza infection. The FimH-mediated antiviral response against influenza virus appears to be partially dependent on alveolar macrophages. The antiviral effects are likely mediated by the innate mediators (TNF-α, IL-12 or RANTES) and/or by activation of a feedback inhibition loop to curtail the pulmonary inflammation possibly be the potential mechanisms involved in FimH-mediated protection. FimH thus holds promise to be a possible prophylactic mean of control against influenza viral infection. |
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| MeSH term(s) | Adhesins, Escherichia coli/administration & dosage ; Adhesins, Escherichia coli/immunology ; Administration, Intranasal ; Animals ; Cell Movement ; Chemokine CCL5/metabolism ; Fimbriae Proteins/administration & dosage ; Fimbriae Proteins/immunology ; Immunity, Innate/drug effects ; Influenza A virus/immunology ; Influenza A virus/pathogenicity ; Interleukin-12/secretion ; Lung/pathology ; Lung/virology ; Macrophages, Alveolar/immunology ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Neutrophils/immunology ; Orthomyxoviridae Infections/immunology ; Orthomyxoviridae Infections/mortality ; Orthomyxoviridae Infections/pathology ; Orthomyxoviridae Infections/prevention & control ; Survival Analysis ; Toll-Like Receptor 4/administration & dosage ; Toll-Like Receptor 4/immunology ; Tumor Necrosis Factor-alpha/secretion | |||||
| Chemical Substances | Adhesins, Escherichia coli ; Chemokine CCL5 ; Tlr4 protein, mouse ; Toll-Like Receptor 4 ; Tumor Necrosis Factor-alpha ; fimH protein, E coli ; Fimbriae Proteins (147680-16-8) ; Interleukin-12 (187348-17-0) | |||||
| Language | English | |||||
| Publishing date | 2011-11 | |||||
| Publishing country | Netherlands | |||||
| Document type | Journal Article ; Research Support, Non-U.S. Gov't | |||||
| ZDB-ID | 306628-9 | |||||
| ISSN | 1872-9096 ; 0166-3542 | |||||
| ISSN (online) | 1872-9096 | |||||
| ISSN | 0166-3542 | |||||
| DOI | 10.1016/j.antiviral.2011.09.004 | |||||
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| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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