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Differential Macrophage Polarization in Male and Female BALB/c Mice Infected With Coxsackievirus B3 Defines Susceptibility to Viral Myocarditis
RATIONAL:Myocardial infiltrating macrophages play an important role in the pathogenesis of viral myocarditis in male BALB/c mice following coxsackievirus B3 (CVB3) infection. Interestingly, comparable macrophage numbers were observed in the myocardium of female mice during acute myocarditis. OBJECTI...
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| Published in: | Circulation research 2009-08, Vol.105 (4), p.353-364 |
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| container_end_page | 364 |
| container_issue | 4 |
| container_start_page | 353 |
| container_title | Circulation research |
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| creator | Li, Kang Xu, Wei Guo, Qiang Jiang, Zhenggang Wang, Ping Yue, Yan Xiong, Sidong |
| description | RATIONAL:Myocardial infiltrating macrophages play an important role in the pathogenesis of viral myocarditis in male BALB/c mice following coxsackievirus B3 (CVB3) infection. Interestingly, comparable macrophage numbers were observed in the myocardium of female mice during acute myocarditis.
OBJECTIVE:Given CVB3 infection causes severe myocarditis in male but not female mice, we postulated that macrophages infiltrating the myocardium of female mice may display distinct functional properties that contribute to differential susceptibility to CVB3 myocarditis.
METHODS AND RESULTS:Here, we found that myocardial infiltrating macrophages from CVB3-infected male mice expressed high levels of classically activated macrophages (M1) markers, including inducible nitric oxide synthase, interleukin-12, tumor necrosis factor-α, and CD16/32, whereas those of females showed enhanced expression of arginase 1, interleukin-10, macrophage mannose receptor (MMR) and macrophage galactose type C-type lectin (MGL) that were associated with alternatively activated macrophage (M2) phenotype. Moreover, distinct myocardial-derived cytokines were found to play a critical role in differential macrophage polarization between sexes after CVB3 infection. Adoptive transfer of ex vivo programmed M1 macrophages, as expectedly, significantly increased myocarditis in both male and female mice. Strikingly, transfer of M2 macrophages into susceptible male mice remarkably alleviated myocardial inflammation by modulating local cytokine profile and promoting peripheral regulatory T cell (Treg) differentiation.
CONCLUSIONS:Taken together, this study may facilitate the understanding of the mechanism underlying gender bias in susceptibility to CVB3 myocarditis and the development of therapeutic strategies based on macrophage polarization for inflammatory heart disease. |
| doi_str_mv | 10.1161/CIRCRESAHA.109.195230 |
| format | article |
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OBJECTIVE:Given CVB3 infection causes severe myocarditis in male but not female mice, we postulated that macrophages infiltrating the myocardium of female mice may display distinct functional properties that contribute to differential susceptibility to CVB3 myocarditis.
METHODS AND RESULTS:Here, we found that myocardial infiltrating macrophages from CVB3-infected male mice expressed high levels of classically activated macrophages (M1) markers, including inducible nitric oxide synthase, interleukin-12, tumor necrosis factor-α, and CD16/32, whereas those of females showed enhanced expression of arginase 1, interleukin-10, macrophage mannose receptor (MMR) and macrophage galactose type C-type lectin (MGL) that were associated with alternatively activated macrophage (M2) phenotype. Moreover, distinct myocardial-derived cytokines were found to play a critical role in differential macrophage polarization between sexes after CVB3 infection. Adoptive transfer of ex vivo programmed M1 macrophages, as expectedly, significantly increased myocarditis in both male and female mice. Strikingly, transfer of M2 macrophages into susceptible male mice remarkably alleviated myocardial inflammation by modulating local cytokine profile and promoting peripheral regulatory T cell (Treg) differentiation.
CONCLUSIONS:Taken together, this study may facilitate the understanding of the mechanism underlying gender bias in susceptibility to CVB3 myocarditis and the development of therapeutic strategies based on macrophage polarization for inflammatory heart disease.</description><identifier>ISSN: 0009-7330</identifier><identifier>EISSN: 1524-4571</identifier><identifier>DOI: 10.1161/CIRCRESAHA.109.195230</identifier><identifier>PMID: 19608981</identifier><identifier>CODEN: CIRUAL</identifier><language>eng</language><publisher>Hagerstown, MD: American Heart Association, Inc</publisher><subject>Adoptive Transfer ; Animals ; Arginase - biosynthesis ; Biological and medical sciences ; Cardiology. Vascular system ; Coxsackievirus Infections - metabolism ; Coxsackievirus Infections - pathology ; Coxsackievirus Infections - virology ; Cytokines - biosynthesis ; Disease Susceptibility - metabolism ; Disease Susceptibility - pathology ; Disease Susceptibility - virology ; Enterovirus B, Human ; Female ; Fundamental and applied biological sciences. Psychology ; Heart ; Lectins, C-Type - biosynthesis ; Macrophage Activation ; Macrophages - metabolism ; Macrophages - pathology ; Macrophages - transplantation ; Macrophages - virology ; Male ; Mannose-Binding Lectins - biosynthesis ; Medical sciences ; Mice ; Mice, Inbred BALB C ; Myocarditis - metabolism ; Myocarditis - pathology ; Myocarditis - virology ; Myocarditis. Cardiomyopathies ; Myocardium - metabolism ; Myocardium - pathology ; Nitric Oxide Synthase Type II - biosynthesis ; Receptors, Cell Surface - biosynthesis ; Receptors, IgG - biosynthesis ; Sex Characteristics ; Vertebrates: cardiovascular system</subject><ispartof>Circulation research, 2009-08, Vol.105 (4), p.353-364</ispartof><rights>2009 American Heart Association, Inc.</rights><rights>2009 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4666-bd2a29d17356f14365ff0902ac097cf01cb93fc7e6078356f6111623cbff38e73</citedby><cites>FETCH-LOGICAL-c4666-bd2a29d17356f14365ff0902ac097cf01cb93fc7e6078356f6111623cbff38e73</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>315,786,790,27957,27958</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=21846111$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/19608981$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Li, Kang</creatorcontrib><creatorcontrib>Xu, Wei</creatorcontrib><creatorcontrib>Guo, Qiang</creatorcontrib><creatorcontrib>Jiang, Zhenggang</creatorcontrib><creatorcontrib>Wang, Ping</creatorcontrib><creatorcontrib>Yue, Yan</creatorcontrib><creatorcontrib>Xiong, Sidong</creatorcontrib><title>Differential Macrophage Polarization in Male and Female BALB/c Mice Infected With Coxsackievirus B3 Defines Susceptibility to Viral Myocarditis</title><title>Circulation research</title><addtitle>Circ Res</addtitle><description>RATIONAL:Myocardial infiltrating macrophages play an important role in the pathogenesis of viral myocarditis in male BALB/c mice following coxsackievirus B3 (CVB3) infection. Interestingly, comparable macrophage numbers were observed in the myocardium of female mice during acute myocarditis.
OBJECTIVE:Given CVB3 infection causes severe myocarditis in male but not female mice, we postulated that macrophages infiltrating the myocardium of female mice may display distinct functional properties that contribute to differential susceptibility to CVB3 myocarditis.
METHODS AND RESULTS:Here, we found that myocardial infiltrating macrophages from CVB3-infected male mice expressed high levels of classically activated macrophages (M1) markers, including inducible nitric oxide synthase, interleukin-12, tumor necrosis factor-α, and CD16/32, whereas those of females showed enhanced expression of arginase 1, interleukin-10, macrophage mannose receptor (MMR) and macrophage galactose type C-type lectin (MGL) that were associated with alternatively activated macrophage (M2) phenotype. Moreover, distinct myocardial-derived cytokines were found to play a critical role in differential macrophage polarization between sexes after CVB3 infection. Adoptive transfer of ex vivo programmed M1 macrophages, as expectedly, significantly increased myocarditis in both male and female mice. Strikingly, transfer of M2 macrophages into susceptible male mice remarkably alleviated myocardial inflammation by modulating local cytokine profile and promoting peripheral regulatory T cell (Treg) differentiation.
CONCLUSIONS:Taken together, this study may facilitate the understanding of the mechanism underlying gender bias in susceptibility to CVB3 myocarditis and the development of therapeutic strategies based on macrophage polarization for inflammatory heart disease.</description><subject>Adoptive Transfer</subject><subject>Animals</subject><subject>Arginase - biosynthesis</subject><subject>Biological and medical sciences</subject><subject>Cardiology. Vascular system</subject><subject>Coxsackievirus Infections - metabolism</subject><subject>Coxsackievirus Infections - pathology</subject><subject>Coxsackievirus Infections - virology</subject><subject>Cytokines - biosynthesis</subject><subject>Disease Susceptibility - metabolism</subject><subject>Disease Susceptibility - pathology</subject><subject>Disease Susceptibility - virology</subject><subject>Enterovirus B, Human</subject><subject>Female</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Heart</subject><subject>Lectins, C-Type - biosynthesis</subject><subject>Macrophage Activation</subject><subject>Macrophages - metabolism</subject><subject>Macrophages - pathology</subject><subject>Macrophages - transplantation</subject><subject>Macrophages - virology</subject><subject>Male</subject><subject>Mannose-Binding Lectins - biosynthesis</subject><subject>Medical sciences</subject><subject>Mice</subject><subject>Mice, Inbred BALB C</subject><subject>Myocarditis - metabolism</subject><subject>Myocarditis - pathology</subject><subject>Myocarditis - virology</subject><subject>Myocarditis. Cardiomyopathies</subject><subject>Myocardium - metabolism</subject><subject>Myocardium - pathology</subject><subject>Nitric Oxide Synthase Type II - biosynthesis</subject><subject>Receptors, Cell Surface - biosynthesis</subject><subject>Receptors, IgG - biosynthesis</subject><subject>Sex Characteristics</subject><subject>Vertebrates: cardiovascular system</subject><issn>0009-7330</issn><issn>1524-4571</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2009</creationdate><recordtype>article</recordtype><recordid>eNpFkdty0zAQhjUMHRoKjwCjG7hzqoMtW5eJ29LMpAPTcrj0yPKKiCp2KsmU8BK8MvIk015pZ_db7e7_I_SOkjmlgp7Xq9v69vJucb2YUyLnVBaMkxdoRguWZ3lR0pdoRgiRWck5OUWvQ_hFCM05k6_QKZWCVLKiM_TvwhoDHvpolcM3Svtht1E_AX8ZnPL2r4p26LHtU8kBVn2Hr2A7hcvFenmu8Y3VgFe9AR2hwz9s3OB6-BOUvrfw2_ox4CXHF2BsDwHfjUHDLtrWOhv3OA74u_XT2P2gle9stOENOjHKBXh7fM_Qt6vLr_V1tv78aVUv1pnOhRBZ2zHFZEdLXgiTrhKFMUQSpjSRpTaE6lZyo0sQpKwmRtCkGuO6NYZXUPIz9PHw784PDyOE2GxtWs451cMwhkaURUVLKhJYHMCkTAgeTLPzdqv8vqGkmZxonp1IKdkcnEh9748DxnYL3XPXUfoEfDgCKmjljFe9tuGJY7TKp6UTlx-4x8FF8OHejY_gmw0oFzdNsphwQlnGktekojnJppTg_wESpKI5</recordid><startdate>20090814</startdate><enddate>20090814</enddate><creator>Li, Kang</creator><creator>Xu, Wei</creator><creator>Guo, Qiang</creator><creator>Jiang, Zhenggang</creator><creator>Wang, Ping</creator><creator>Yue, Yan</creator><creator>Xiong, Sidong</creator><general>American Heart Association, Inc</general><general>Lippincott Williams & Wilkins</general><scope>IQODW</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>7X8</scope></search><sort><creationdate>20090814</creationdate><title>Differential Macrophage Polarization in Male and Female BALB/c Mice Infected With Coxsackievirus B3 Defines Susceptibility to Viral Myocarditis</title><author>Li, Kang ; Xu, Wei ; Guo, Qiang ; Jiang, Zhenggang ; Wang, Ping ; Yue, Yan ; Xiong, Sidong</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4666-bd2a29d17356f14365ff0902ac097cf01cb93fc7e6078356f6111623cbff38e73</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2009</creationdate><topic>Adoptive Transfer</topic><topic>Animals</topic><topic>Arginase - biosynthesis</topic><topic>Biological and medical sciences</topic><topic>Cardiology. Vascular system</topic><topic>Coxsackievirus Infections - metabolism</topic><topic>Coxsackievirus Infections - pathology</topic><topic>Coxsackievirus Infections - virology</topic><topic>Cytokines - biosynthesis</topic><topic>Disease Susceptibility - metabolism</topic><topic>Disease Susceptibility - pathology</topic><topic>Disease Susceptibility - virology</topic><topic>Enterovirus B, Human</topic><topic>Female</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Heart</topic><topic>Lectins, C-Type - biosynthesis</topic><topic>Macrophage Activation</topic><topic>Macrophages - metabolism</topic><topic>Macrophages - pathology</topic><topic>Macrophages - transplantation</topic><topic>Macrophages - virology</topic><topic>Male</topic><topic>Mannose-Binding Lectins - biosynthesis</topic><topic>Medical sciences</topic><topic>Mice</topic><topic>Mice, Inbred BALB C</topic><topic>Myocarditis - metabolism</topic><topic>Myocarditis - pathology</topic><topic>Myocarditis - virology</topic><topic>Myocarditis. Cardiomyopathies</topic><topic>Myocardium - metabolism</topic><topic>Myocardium - pathology</topic><topic>Nitric Oxide Synthase Type II - biosynthesis</topic><topic>Receptors, Cell Surface - biosynthesis</topic><topic>Receptors, IgG - biosynthesis</topic><topic>Sex Characteristics</topic><topic>Vertebrates: cardiovascular system</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Li, Kang</creatorcontrib><creatorcontrib>Xu, Wei</creatorcontrib><creatorcontrib>Guo, Qiang</creatorcontrib><creatorcontrib>Jiang, Zhenggang</creatorcontrib><creatorcontrib>Wang, Ping</creatorcontrib><creatorcontrib>Yue, Yan</creatorcontrib><creatorcontrib>Xiong, Sidong</creatorcontrib><collection>Pascal-Francis</collection><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><jtitle>Circulation research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Li, Kang</au><au>Xu, Wei</au><au>Guo, Qiang</au><au>Jiang, Zhenggang</au><au>Wang, Ping</au><au>Yue, Yan</au><au>Xiong, Sidong</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Differential Macrophage Polarization in Male and Female BALB/c Mice Infected With Coxsackievirus B3 Defines Susceptibility to Viral Myocarditis</atitle><jtitle>Circulation research</jtitle><addtitle>Circ Res</addtitle><date>2009-08-14</date><risdate>2009</risdate><volume>105</volume><issue>4</issue><spage>353</spage><epage>364</epage><pages>353-364</pages><issn>0009-7330</issn><eissn>1524-4571</eissn><coden>CIRUAL</coden><notes>ObjectType-Article-1</notes><notes>SourceType-Scholarly Journals-1</notes><notes>ObjectType-Feature-2</notes><notes>content type line 23</notes><abstract>RATIONAL:Myocardial infiltrating macrophages play an important role in the pathogenesis of viral myocarditis in male BALB/c mice following coxsackievirus B3 (CVB3) infection. Interestingly, comparable macrophage numbers were observed in the myocardium of female mice during acute myocarditis.
OBJECTIVE:Given CVB3 infection causes severe myocarditis in male but not female mice, we postulated that macrophages infiltrating the myocardium of female mice may display distinct functional properties that contribute to differential susceptibility to CVB3 myocarditis.
METHODS AND RESULTS:Here, we found that myocardial infiltrating macrophages from CVB3-infected male mice expressed high levels of classically activated macrophages (M1) markers, including inducible nitric oxide synthase, interleukin-12, tumor necrosis factor-α, and CD16/32, whereas those of females showed enhanced expression of arginase 1, interleukin-10, macrophage mannose receptor (MMR) and macrophage galactose type C-type lectin (MGL) that were associated with alternatively activated macrophage (M2) phenotype. Moreover, distinct myocardial-derived cytokines were found to play a critical role in differential macrophage polarization between sexes after CVB3 infection. Adoptive transfer of ex vivo programmed M1 macrophages, as expectedly, significantly increased myocarditis in both male and female mice. Strikingly, transfer of M2 macrophages into susceptible male mice remarkably alleviated myocardial inflammation by modulating local cytokine profile and promoting peripheral regulatory T cell (Treg) differentiation.
CONCLUSIONS:Taken together, this study may facilitate the understanding of the mechanism underlying gender bias in susceptibility to CVB3 myocarditis and the development of therapeutic strategies based on macrophage polarization for inflammatory heart disease.</abstract><cop>Hagerstown, MD</cop><pub>American Heart Association, Inc</pub><pmid>19608981</pmid><doi>10.1161/CIRCRESAHA.109.195230</doi><tpages>12</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Adoptive Transfer Animals Arginase - biosynthesis Biological and medical sciences Cardiology. Vascular system Coxsackievirus Infections - metabolism Coxsackievirus Infections - pathology Coxsackievirus Infections - virology Cytokines - biosynthesis Disease Susceptibility - metabolism Disease Susceptibility - pathology Disease Susceptibility - virology Enterovirus B, Human Female Fundamental and applied biological sciences. Psychology Heart Lectins, C-Type - biosynthesis Macrophage Activation Macrophages - metabolism Macrophages - pathology Macrophages - transplantation Macrophages - virology Male Mannose-Binding Lectins - biosynthesis Medical sciences Mice Mice, Inbred BALB C Myocarditis - metabolism Myocarditis - pathology Myocarditis - virology Myocarditis. Cardiomyopathies Myocardium - metabolism Myocardium - pathology Nitric Oxide Synthase Type II - biosynthesis Receptors, Cell Surface - biosynthesis Receptors, IgG - biosynthesis Sex Characteristics Vertebrates: cardiovascular system |
| title | Differential Macrophage Polarization in Male and Female BALB/c Mice Infected With Coxsackievirus B3 Defines Susceptibility to Viral Myocarditis |
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