Adenoviral infection induces a multi-faceted innate cellular immune response that is mediated by the toll-like receptor pathway in A549 cells
Abstract Adenovirus vectors are known to induce certain genes and impact innate response networks, but a broad understanding of this process and its mechanisms is currently lacking. For this reason, we chose to investigate and characterize Ad innate immunity using homogeneous, primary MEF cells repl...
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Veröffentlicht in: | Virology (New York, N.Y.) N.Y.), 2007-02, Vol.358 (2), p.357-372 |
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description | Abstract Adenovirus vectors are known to induce certain genes and impact innate response networks, but a broad understanding of this process and its mechanisms is currently lacking. For this reason, we chose to investigate and characterize Ad innate immunity using homogeneous, primary MEF cells replete with all the elements of the pathogen-sensing Toll-Like Receptor (TLR) pathway. By using an array-based approach to maximally define transcriptome changes induced upon Ad vector infection, we discovered that Ad infection induces a potent gene and transcription factor network response. This response is characterized by significant changes in the expression of genes involved in focal adhesion, tight junction, and RNA regulation, in addition to TLR pathway and other innate sensing genes. Further investigation using human A549 cells knocked down for various TLR pathway adaptors, revealed significant impacts on the Ad initiation of NF-kB and interferon responses, thus confirming TLR involvement in Ad-mediated immunity across diverse species. |
doi_str_mv | 10.1016/j.virol.2006.08.041 |
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For this reason, we chose to investigate and characterize Ad innate immunity using homogeneous, primary MEF cells replete with all the elements of the pathogen-sensing Toll-Like Receptor (TLR) pathway. By using an array-based approach to maximally define transcriptome changes induced upon Ad vector infection, we discovered that Ad infection induces a potent gene and transcription factor network response. This response is characterized by significant changes in the expression of genes involved in focal adhesion, tight junction, and RNA regulation, in addition to TLR pathway and other innate sensing genes. 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For this reason, we chose to investigate and characterize Ad innate immunity using homogeneous, primary MEF cells replete with all the elements of the pathogen-sensing Toll-Like Receptor (TLR) pathway. By using an array-based approach to maximally define transcriptome changes induced upon Ad vector infection, we discovered that Ad infection induces a potent gene and transcription factor network response. This response is characterized by significant changes in the expression of genes involved in focal adhesion, tight junction, and RNA regulation, in addition to TLR pathway and other innate sensing genes. Further investigation using human A549 cells knocked down for various TLR pathway adaptors, revealed significant impacts on the Ad initiation of NF-kB and interferon responses, thus confirming TLR involvement in Ad-mediated immunity across diverse species.</description><subject>Adenoviridae - genetics</subject><subject>Adenoviridae Infections - immunology</subject><subject>Adenovirus</subject><subject>Animals</subject><subject>Cell Line, Tumor</subject><subject>Cells, Cultured</subject><subject>Cytokines - biosynthesis</subject><subject>Cytokines - genetics</subject><subject>Fibroblasts - immunology</subject><subject>Gene Expression Profiling</subject><subject>Genetic Vectors - genetics</subject><subject>Humans</subject><subject>Immunity, Innate - genetics</subject><subject>Infectious Disease</subject><subject>Innate immune response</subject><subject>Interferons - genetics</subject><subject>Interferons - metabolism</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Microarray</subject><subject>NF-kappa B - genetics</subject><subject>NF-kappa B - metabolism</subject><subject>Oligonucleotide Array Sequence Analysis</subject><subject>Toll-like receptor</subject><subject>Toll-Like Receptors - physiology</subject><subject>Transduction, Genetic</subject><issn>0042-6822</issn><issn>1096-0341</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2007</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFUk2LFDEQDaK44-ovECQnb91WPrrTfVAYFnUXFjyo55BJV7OZTXfGJL0yP8L_bHpnQPCyEEiqeO9VeK8IecugZsDaD_v6wcXgaw7Q1tDVINkzsmHQtxUIyZ6TDYDkVdtxfkFepbSHUisFL8kFU8AVtLAhf7YDzqEIGU_dPKLNLszlNSwWEzV0Wnx21WgsZhxKfzYZqUXvF28iddO0zEgjpkOYE9J8ZzJ1iU44OLMSdsfSK_3gfeXd_Qq1eMgh0oPJd7_NsUjSbSP7R830mrwYjU_45nxfkp9fPv-4uq5uv329udreVlZKkathEEqNfMDBmNZKC4Bqt2OIINGYninZGN4hMNXYkQnsR2t6ENwo3otOduKSvD_pHmL4tWDKenJp_YGZMSxJt13fyE6KJ4EcRMNYvyqKE9DGkFLEUR-im0w8agZ6jUvv9WNceo1LQ6dLXIX17iy_7Ipn_zjnfArg4wmAxY0Hh1En63C2xd_iZNZDcE8M-PQf33o3O2v8PR4x7cMS52K0ZjpxDfr7ujHrwpTZ5UgQfwHgVb5r</recordid><startdate>20070220</startdate><enddate>20070220</enddate><creator>Hartman, Zachary C</creator><creator>Black, Esther P</creator><creator>Amalfitano, Andrea</creator><general>Elsevier Inc</general><scope>6I.</scope><scope>AAFTH</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7U9</scope><scope>H94</scope><scope>7X8</scope></search><sort><creationdate>20070220</creationdate><title>Adenoviral infection induces a multi-faceted innate cellular immune response that is mediated by the toll-like receptor pathway in A549 cells</title><author>Hartman, Zachary C ; Black, Esther P ; Amalfitano, Andrea</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c443t-dd377f2dedaa6c4c00e7bb1ee04eaa91745a28e0175cf13e9fca9032a72938483</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2007</creationdate><topic>Adenoviridae - genetics</topic><topic>Adenoviridae Infections - immunology</topic><topic>Adenovirus</topic><topic>Animals</topic><topic>Cell Line, Tumor</topic><topic>Cells, Cultured</topic><topic>Cytokines - biosynthesis</topic><topic>Cytokines - genetics</topic><topic>Fibroblasts - immunology</topic><topic>Gene Expression Profiling</topic><topic>Genetic Vectors - genetics</topic><topic>Humans</topic><topic>Immunity, Innate - genetics</topic><topic>Infectious Disease</topic><topic>Innate immune response</topic><topic>Interferons - genetics</topic><topic>Interferons - metabolism</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Microarray</topic><topic>NF-kappa B - genetics</topic><topic>NF-kappa B - metabolism</topic><topic>Oligonucleotide Array Sequence Analysis</topic><topic>Toll-like receptor</topic><topic>Toll-Like Receptors - physiology</topic><topic>Transduction, Genetic</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Hartman, Zachary C</creatorcontrib><creatorcontrib>Black, Esther P</creatorcontrib><creatorcontrib>Amalfitano, Andrea</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Virology and AIDS Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Virology (New York, N.Y.)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Hartman, Zachary C</au><au>Black, Esther P</au><au>Amalfitano, Andrea</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Adenoviral infection induces a multi-faceted innate cellular immune response that is mediated by the toll-like receptor pathway in A549 cells</atitle><jtitle>Virology (New York, N.Y.)</jtitle><addtitle>Virology</addtitle><date>2007-02-20</date><risdate>2007</risdate><volume>358</volume><issue>2</issue><spage>357</spage><epage>372</epage><pages>357-372</pages><issn>0042-6822</issn><eissn>1096-0341</eissn><abstract>Abstract Adenovirus vectors are known to induce certain genes and impact innate response networks, but a broad understanding of this process and its mechanisms is currently lacking. For this reason, we chose to investigate and characterize Ad innate immunity using homogeneous, primary MEF cells replete with all the elements of the pathogen-sensing Toll-Like Receptor (TLR) pathway. By using an array-based approach to maximally define transcriptome changes induced upon Ad vector infection, we discovered that Ad infection induces a potent gene and transcription factor network response. This response is characterized by significant changes in the expression of genes involved in focal adhesion, tight junction, and RNA regulation, in addition to TLR pathway and other innate sensing genes. 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subjects | Adenoviridae - genetics Adenoviridae Infections - immunology Adenovirus Animals Cell Line, Tumor Cells, Cultured Cytokines - biosynthesis Cytokines - genetics Fibroblasts - immunology Gene Expression Profiling Genetic Vectors - genetics Humans Immunity, Innate - genetics Infectious Disease Innate immune response Interferons - genetics Interferons - metabolism Mice Mice, Inbred C57BL Microarray NF-kappa B - genetics NF-kappa B - metabolism Oligonucleotide Array Sequence Analysis Toll-like receptor Toll-Like Receptors - physiology Transduction, Genetic |
title | Adenoviral infection induces a multi-faceted innate cellular immune response that is mediated by the toll-like receptor pathway in A549 cells |
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