Chemokine receptor Ccr2 is critical for monocyte accumulation and survival in West Nile virus encephalitis
West Nile virus (WNV) is a re-emerging pathogen responsible for outbreaks of fatal meningoencephalitis in humans. Previous studies have suggested a protective role for monocytes in a mouse model of WNV infection, but the molecular mechanisms have remained unclear. In this study, we show that genetic...
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| Veröffentlicht in: | The Journal of immunology (1950) 2011-01, Vol.186 (1), p.471-478 |
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| creator | Lim, Jean K Obara, Christopher J Rivollier, Aymeric Pletnev, Alexander G Kelsall, Brian L Murphy, Philip M |
| description | West Nile virus (WNV) is a re-emerging pathogen responsible for outbreaks of fatal meningoencephalitis in humans. Previous studies have suggested a protective role for monocytes in a mouse model of WNV infection, but the molecular mechanisms have remained unclear. In this study, we show that genetic deficiency in Ccr2, a chemokine receptor on Ly6c(hi) inflammatory monocytes and other leukocyte subtypes, markedly increases mortality due to WNV encephalitis in C57BL/6 mice; this was associated with a large and selective reduction of Ly6c(hi) monocyte accumulation in the brain. WNV infection in Ccr2(+/+) mice induced a strong and highly selective monocytosis in peripheral blood that was absent in Ccr2(-/-) mice, which in contrast showed sustained monocytopenia. When a 1:1 mixture of Ccr2(+/+) and Ccr2(-/-) donor monocytes was transferred by vein into WNV-infected Ccr2(-/-) recipient mice, monocyte accumulation in the CNS was not skewed toward either component of the mixture, indicating that Ccr2 is not required for trafficking of monocytes from blood to brain. We conclude that Ccr2 mediates highly selective peripheral blood monocytosis during WNV infection of mice and that this is critical for accumulation of monocytes in the brain. |
| doi_str_mv | 10.4049/jimmunol.1003003 |
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Previous studies have suggested a protective role for monocytes in a mouse model of WNV infection, but the molecular mechanisms have remained unclear. In this study, we show that genetic deficiency in Ccr2, a chemokine receptor on Ly6c(hi) inflammatory monocytes and other leukocyte subtypes, markedly increases mortality due to WNV encephalitis in C57BL/6 mice; this was associated with a large and selective reduction of Ly6c(hi) monocyte accumulation in the brain. WNV infection in Ccr2(+/+) mice induced a strong and highly selective monocytosis in peripheral blood that was absent in Ccr2(-/-) mice, which in contrast showed sustained monocytopenia. When a 1:1 mixture of Ccr2(+/+) and Ccr2(-/-) donor monocytes was transferred by vein into WNV-infected Ccr2(-/-) recipient mice, monocyte accumulation in the CNS was not skewed toward either component of the mixture, indicating that Ccr2 is not required for trafficking of monocytes from blood to brain. We conclude that Ccr2 mediates highly selective peripheral blood monocytosis during WNV infection of mice and that this is critical for accumulation of monocytes in the brain.</description><identifier>ISSN: 0022-1767</identifier><identifier>EISSN: 1550-6606</identifier><identifier>DOI: 10.4049/jimmunol.1003003</identifier><identifier>PMID: 21131425</identifier><language>eng</language><publisher>United States</publisher><subject>Animals ; Cell Survival - genetics ; Cell Survival - immunology ; Chemotaxis, Leukocyte - genetics ; Chemotaxis, Leukocyte - immunology ; Chlorocebus aethiops ; Disease Models, Animal ; Humans ; Leukocytosis - immunology ; Leukocytosis - pathology ; Leukocytosis - virology ; Leukopenia - immunology ; Leukopenia - pathology ; Leukopenia - virology ; Ligands ; Melanoma, Experimental - immunology ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Monocytes - immunology ; Monocytes - metabolism ; Monocytes - pathology ; Receptors, CCR2 - deficiency ; Receptors, CCR2 - genetics ; Receptors, CCR2 - metabolism ; Receptors, CCR2 - physiology ; Vero Cells ; Viral Load - genetics ; Viral Load - immunology ; West Nile Fever - immunology ; West Nile Fever - mortality ; West Nile Fever - pathology ; West Nile virus ; West Nile virus - immunology</subject><ispartof>The Journal of immunology (1950), 2011-01, Vol.186 (1), p.471-478</ispartof><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c493t-fca41309195388a36258527ca3ee87dca233296f3577800c4a56d4b8deec38393</citedby><cites>FETCH-LOGICAL-c493t-fca41309195388a36258527ca3ee87dca233296f3577800c4a56d4b8deec38393</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,776,780,881,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/21131425$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Lim, Jean K</creatorcontrib><creatorcontrib>Obara, Christopher J</creatorcontrib><creatorcontrib>Rivollier, Aymeric</creatorcontrib><creatorcontrib>Pletnev, Alexander G</creatorcontrib><creatorcontrib>Kelsall, Brian L</creatorcontrib><creatorcontrib>Murphy, Philip M</creatorcontrib><title>Chemokine receptor Ccr2 is critical for monocyte accumulation and survival in West Nile virus encephalitis</title><title>The Journal of immunology (1950)</title><addtitle>J Immunol</addtitle><description>West Nile virus (WNV) is a re-emerging pathogen responsible for outbreaks of fatal meningoencephalitis in humans. Previous studies have suggested a protective role for monocytes in a mouse model of WNV infection, but the molecular mechanisms have remained unclear. In this study, we show that genetic deficiency in Ccr2, a chemokine receptor on Ly6c(hi) inflammatory monocytes and other leukocyte subtypes, markedly increases mortality due to WNV encephalitis in C57BL/6 mice; this was associated with a large and selective reduction of Ly6c(hi) monocyte accumulation in the brain. WNV infection in Ccr2(+/+) mice induced a strong and highly selective monocytosis in peripheral blood that was absent in Ccr2(-/-) mice, which in contrast showed sustained monocytopenia. When a 1:1 mixture of Ccr2(+/+) and Ccr2(-/-) donor monocytes was transferred by vein into WNV-infected Ccr2(-/-) recipient mice, monocyte accumulation in the CNS was not skewed toward either component of the mixture, indicating that Ccr2 is not required for trafficking of monocytes from blood to brain. We conclude that Ccr2 mediates highly selective peripheral blood monocytosis during WNV infection of mice and that this is critical for accumulation of monocytes in the brain.</description><subject>Animals</subject><subject>Cell Survival - genetics</subject><subject>Cell Survival - immunology</subject><subject>Chemotaxis, Leukocyte - genetics</subject><subject>Chemotaxis, Leukocyte - immunology</subject><subject>Chlorocebus aethiops</subject><subject>Disease Models, Animal</subject><subject>Humans</subject><subject>Leukocytosis - immunology</subject><subject>Leukocytosis - pathology</subject><subject>Leukocytosis - virology</subject><subject>Leukopenia - immunology</subject><subject>Leukopenia - pathology</subject><subject>Leukopenia - virology</subject><subject>Ligands</subject><subject>Melanoma, Experimental - immunology</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Mice, Knockout</subject><subject>Monocytes - immunology</subject><subject>Monocytes - metabolism</subject><subject>Monocytes - pathology</subject><subject>Receptors, CCR2 - deficiency</subject><subject>Receptors, CCR2 - genetics</subject><subject>Receptors, CCR2 - metabolism</subject><subject>Receptors, CCR2 - physiology</subject><subject>Vero Cells</subject><subject>Viral Load - genetics</subject><subject>Viral Load - immunology</subject><subject>West Nile Fever - immunology</subject><subject>West Nile Fever - mortality</subject><subject>West Nile Fever - pathology</subject><subject>West Nile virus</subject><subject>West Nile virus - immunology</subject><issn>0022-1767</issn><issn>1550-6606</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkU2LFDEQhoMo7uzq3ZPk5qnXynf3RZBh1YVFL4rHkE1XOxnTyZh0D-y_N7Kzi56EQEHqrYcqHkJeMbiUIIe3-zDPa8rxkgGI9p6QDVMKOq1BPyUbAM47ZrQ5I-e17gFAA5fPyRlnTDDJ1Ybstzuc88-QkBb0eFhyoVtfOA2V-hKW4F2kU_ucc8r-bkHqvF_nNbol5ERdGmldyzEcWywk-h3rQj-HiPQYyloppsbcudhA9QV5NrlY8eWpXpBvH66-bj91N18-Xm_f33ReDmLpJu8kEzCwQYm-d0Jz1StuvBOIvRm940LwQU9CGdMDeOmUHuVtPyJ60YtBXJB399zDejvj6DEtxUV7KGF25c5mF-y_nRR29kc-WiGBC6ka4M0JUPKvtV1k51A9xugS5rXaXmljJAzi_0kOZmgCdEvCfdKXXGvB6XEfBvaPS_vg0p5ctpHXf9_xOPAgT_wGRtueSA</recordid><startdate>20110101</startdate><enddate>20110101</enddate><creator>Lim, Jean K</creator><creator>Obara, Christopher J</creator><creator>Rivollier, Aymeric</creator><creator>Pletnev, Alexander G</creator><creator>Kelsall, Brian L</creator><creator>Murphy, Philip M</creator><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>7X8</scope><scope>7T5</scope><scope>7TK</scope><scope>7U7</scope><scope>7U9</scope><scope>C1K</scope><scope>H94</scope><scope>5PM</scope></search><sort><creationdate>20110101</creationdate><title>Chemokine receptor Ccr2 is critical for monocyte accumulation and survival in West Nile virus encephalitis</title><author>Lim, Jean K ; Obara, Christopher J ; Rivollier, Aymeric ; Pletnev, Alexander G ; Kelsall, Brian L ; Murphy, Philip M</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c493t-fca41309195388a36258527ca3ee87dca233296f3577800c4a56d4b8deec38393</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2011</creationdate><topic>Animals</topic><topic>Cell Survival - genetics</topic><topic>Cell Survival - immunology</topic><topic>Chemotaxis, Leukocyte - genetics</topic><topic>Chemotaxis, Leukocyte - immunology</topic><topic>Chlorocebus aethiops</topic><topic>Disease Models, Animal</topic><topic>Humans</topic><topic>Leukocytosis - immunology</topic><topic>Leukocytosis - pathology</topic><topic>Leukocytosis - virology</topic><topic>Leukopenia - immunology</topic><topic>Leukopenia - pathology</topic><topic>Leukopenia - virology</topic><topic>Ligands</topic><topic>Melanoma, Experimental - immunology</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Mice, Knockout</topic><topic>Monocytes - immunology</topic><topic>Monocytes - metabolism</topic><topic>Monocytes - pathology</topic><topic>Receptors, CCR2 - deficiency</topic><topic>Receptors, CCR2 - genetics</topic><topic>Receptors, CCR2 - metabolism</topic><topic>Receptors, CCR2 - physiology</topic><topic>Vero Cells</topic><topic>Viral Load - genetics</topic><topic>Viral Load - immunology</topic><topic>West Nile Fever - immunology</topic><topic>West Nile Fever - mortality</topic><topic>West Nile Fever - pathology</topic><topic>West Nile virus</topic><topic>West Nile virus - immunology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Lim, Jean K</creatorcontrib><creatorcontrib>Obara, Christopher J</creatorcontrib><creatorcontrib>Rivollier, Aymeric</creatorcontrib><creatorcontrib>Pletnev, Alexander G</creatorcontrib><creatorcontrib>Kelsall, Brian L</creatorcontrib><creatorcontrib>Murphy, Philip M</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>Immunology Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Environmental Sciences and Pollution Management</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>The Journal of immunology (1950)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Lim, Jean K</au><au>Obara, Christopher J</au><au>Rivollier, Aymeric</au><au>Pletnev, Alexander G</au><au>Kelsall, Brian L</au><au>Murphy, Philip M</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Chemokine receptor Ccr2 is critical for monocyte accumulation and survival in West Nile virus encephalitis</atitle><jtitle>The Journal of immunology (1950)</jtitle><addtitle>J Immunol</addtitle><date>2011-01-01</date><risdate>2011</risdate><volume>186</volume><issue>1</issue><spage>471</spage><epage>478</epage><pages>471-478</pages><issn>0022-1767</issn><eissn>1550-6606</eissn><abstract>West Nile virus (WNV) is a re-emerging pathogen responsible for outbreaks of fatal meningoencephalitis in humans. Previous studies have suggested a protective role for monocytes in a mouse model of WNV infection, but the molecular mechanisms have remained unclear. In this study, we show that genetic deficiency in Ccr2, a chemokine receptor on Ly6c(hi) inflammatory monocytes and other leukocyte subtypes, markedly increases mortality due to WNV encephalitis in C57BL/6 mice; this was associated with a large and selective reduction of Ly6c(hi) monocyte accumulation in the brain. WNV infection in Ccr2(+/+) mice induced a strong and highly selective monocytosis in peripheral blood that was absent in Ccr2(-/-) mice, which in contrast showed sustained monocytopenia. When a 1:1 mixture of Ccr2(+/+) and Ccr2(-/-) donor monocytes was transferred by vein into WNV-infected Ccr2(-/-) recipient mice, monocyte accumulation in the CNS was not skewed toward either component of the mixture, indicating that Ccr2 is not required for trafficking of monocytes from blood to brain. 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| subjects | Animals Cell Survival - genetics Cell Survival - immunology Chemotaxis, Leukocyte - genetics Chemotaxis, Leukocyte - immunology Chlorocebus aethiops Disease Models, Animal Humans Leukocytosis - immunology Leukocytosis - pathology Leukocytosis - virology Leukopenia - immunology Leukopenia - pathology Leukopenia - virology Ligands Melanoma, Experimental - immunology Mice Mice, Inbred C57BL Mice, Knockout Monocytes - immunology Monocytes - metabolism Monocytes - pathology Receptors, CCR2 - deficiency Receptors, CCR2 - genetics Receptors, CCR2 - metabolism Receptors, CCR2 - physiology Vero Cells Viral Load - genetics Viral Load - immunology West Nile Fever - immunology West Nile Fever - mortality West Nile Fever - pathology West Nile virus West Nile virus - immunology |
| title | Chemokine receptor Ccr2 is critical for monocyte accumulation and survival in West Nile virus encephalitis |
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