Mice deficient in ficolin, a lectin complement pathway recognition molecule, are susceptible to Streptococcus pneumoniae infection
Mannose-binding lectin (MBL) and ficolin are complexed with MBL-associated serine proteases, key enzymes of complement activation via the lectin pathway, and act as soluble pattern recognition molecules in the innate immune system. Although numerous reports have revealed the importance of MBL in inf...
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| Veröffentlicht in: | The Journal of immunology (1950) 2012-12, Vol.189 (12), p.5860-5866 |
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| container_title | The Journal of immunology (1950) |
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| creator | Endo, Yuichi Takahashi, Minoru Iwaki, Daisuke Ishida, Yumi Nakazawa, Naomi Kodama, Toshihisa Matsuzaka, Tomohiro Kanno, Kazuko Liu, Yu Tsuchiya, Kohsuke Kawamura, Ikuo Ikawa, Masahito Waguri, Satoshi Wada, Ikuo Matsushita, Misao Schwaeble, Wilhelm J Fujita, Teizo |
| description | Mannose-binding lectin (MBL) and ficolin are complexed with MBL-associated serine proteases, key enzymes of complement activation via the lectin pathway, and act as soluble pattern recognition molecules in the innate immune system. Although numerous reports have revealed the importance of MBL in infectious diseases and autoimmune disorders, the role of ficolin is still unclear. To define the specific role of ficolin in vivo, we generated model mice deficient in ficolins. The ficolin A (FcnA)-deficient (Fcna(-/-)) and FcnA/ficolin B double-deficient (Fcna(-/-)b(-/-)) mice lacked FcnA-mediated complement activation in the sera, because of the absence of complexes comprising FcnA and MBL-associated serine proteases. When the host defense was evaluated by transnasal infection with a Streptococcus pneumoniae strain, which was recognized by ficolins, but not by MBLs, the survival rate was significantly reduced in all three ficolin-deficient (Fcna(-/-), Fcnb(-/-), and Fcna(-/-)b(-/-)) mice compared with wild-type mice. Reconstitution of the FcnA-mediated lectin pathway in vivo improved survival rate in Fcna(-/-) but not in Fcna(-/-)b(-/-) mice, suggesting that both FcnA and ficolin B are essential in defense against S. pneumoniae. These results suggest that ficolins play a crucial role in innate immunity against pneumococcal infection through the lectin complement pathway. |
| doi_str_mv | 10.4049/jimmunol.1200836 |
| format | Article |
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Although numerous reports have revealed the importance of MBL in infectious diseases and autoimmune disorders, the role of ficolin is still unclear. To define the specific role of ficolin in vivo, we generated model mice deficient in ficolins. The ficolin A (FcnA)-deficient (Fcna(-/-)) and FcnA/ficolin B double-deficient (Fcna(-/-)b(-/-)) mice lacked FcnA-mediated complement activation in the sera, because of the absence of complexes comprising FcnA and MBL-associated serine proteases. When the host defense was evaluated by transnasal infection with a Streptococcus pneumoniae strain, which was recognized by ficolins, but not by MBLs, the survival rate was significantly reduced in all three ficolin-deficient (Fcna(-/-), Fcnb(-/-), and Fcna(-/-)b(-/-)) mice compared with wild-type mice. Reconstitution of the FcnA-mediated lectin pathway in vivo improved survival rate in Fcna(-/-) but not in Fcna(-/-)b(-/-) mice, suggesting that both FcnA and ficolin B are essential in defense against S. pneumoniae. These results suggest that ficolins play a crucial role in innate immunity against pneumococcal infection through the lectin complement pathway.</description><identifier>ISSN: 0022-1767</identifier><identifier>EISSN: 1550-6606</identifier><identifier>DOI: 10.4049/jimmunol.1200836</identifier><identifier>PMID: 23150716</identifier><language>eng</language><publisher>United States</publisher><subject>Animals ; CHO Cells ; Complement Activation - genetics ; Complement Activation - immunology ; Complement Pathway, Mannose-Binding Lectin - genetics ; Cricetinae ; Ficolins ; Genetic Predisposition to Disease ; Lectins - deficiency ; Lectins - genetics ; Mannose-Binding Protein-Associated Serine Proteases - deficiency ; Mannose-Binding Protein-Associated Serine Proteases - genetics ; Mice ; Mice, 129 Strain ; Mice, Inbred C57BL ; Mice, Knockout ; Mice, Transgenic ; Pneumonia, Pneumococcal - enzymology ; Pneumonia, Pneumococcal - genetics ; Pneumonia, Pneumococcal - immunology ; Streptococcus pneumoniae ; Streptococcus pneumoniae - genetics ; Streptococcus pneumoniae - immunology</subject><ispartof>The Journal of immunology (1950), 2012-12, Vol.189 (12), p.5860-5866</ispartof><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c440t-be07b3d9beb704cb2e5d9b310f381afe1a9778b542ca6c4bf426557d2a0018f83</citedby><cites>FETCH-LOGICAL-c440t-be07b3d9beb704cb2e5d9b310f381afe1a9778b542ca6c4bf426557d2a0018f83</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,777,781,27905,27906</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23150716$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Endo, Yuichi</creatorcontrib><creatorcontrib>Takahashi, Minoru</creatorcontrib><creatorcontrib>Iwaki, Daisuke</creatorcontrib><creatorcontrib>Ishida, Yumi</creatorcontrib><creatorcontrib>Nakazawa, Naomi</creatorcontrib><creatorcontrib>Kodama, Toshihisa</creatorcontrib><creatorcontrib>Matsuzaka, Tomohiro</creatorcontrib><creatorcontrib>Kanno, Kazuko</creatorcontrib><creatorcontrib>Liu, Yu</creatorcontrib><creatorcontrib>Tsuchiya, Kohsuke</creatorcontrib><creatorcontrib>Kawamura, Ikuo</creatorcontrib><creatorcontrib>Ikawa, Masahito</creatorcontrib><creatorcontrib>Waguri, Satoshi</creatorcontrib><creatorcontrib>Wada, Ikuo</creatorcontrib><creatorcontrib>Matsushita, Misao</creatorcontrib><creatorcontrib>Schwaeble, Wilhelm J</creatorcontrib><creatorcontrib>Fujita, Teizo</creatorcontrib><title>Mice deficient in ficolin, a lectin complement pathway recognition molecule, are susceptible to Streptococcus pneumoniae infection</title><title>The Journal of immunology (1950)</title><addtitle>J Immunol</addtitle><description>Mannose-binding lectin (MBL) and ficolin are complexed with MBL-associated serine proteases, key enzymes of complement activation via the lectin pathway, and act as soluble pattern recognition molecules in the innate immune system. Although numerous reports have revealed the importance of MBL in infectious diseases and autoimmune disorders, the role of ficolin is still unclear. To define the specific role of ficolin in vivo, we generated model mice deficient in ficolins. The ficolin A (FcnA)-deficient (Fcna(-/-)) and FcnA/ficolin B double-deficient (Fcna(-/-)b(-/-)) mice lacked FcnA-mediated complement activation in the sera, because of the absence of complexes comprising FcnA and MBL-associated serine proteases. When the host defense was evaluated by transnasal infection with a Streptococcus pneumoniae strain, which was recognized by ficolins, but not by MBLs, the survival rate was significantly reduced in all three ficolin-deficient (Fcna(-/-), Fcnb(-/-), and Fcna(-/-)b(-/-)) mice compared with wild-type mice. Reconstitution of the FcnA-mediated lectin pathway in vivo improved survival rate in Fcna(-/-) but not in Fcna(-/-)b(-/-) mice, suggesting that both FcnA and ficolin B are essential in defense against S. pneumoniae. These results suggest that ficolins play a crucial role in innate immunity against pneumococcal infection through the lectin complement pathway.</description><subject>Animals</subject><subject>CHO Cells</subject><subject>Complement Activation - genetics</subject><subject>Complement Activation - immunology</subject><subject>Complement Pathway, Mannose-Binding Lectin - genetics</subject><subject>Cricetinae</subject><subject>Ficolins</subject><subject>Genetic Predisposition to Disease</subject><subject>Lectins - deficiency</subject><subject>Lectins - genetics</subject><subject>Mannose-Binding Protein-Associated Serine Proteases - deficiency</subject><subject>Mannose-Binding Protein-Associated Serine Proteases - genetics</subject><subject>Mice</subject><subject>Mice, 129 Strain</subject><subject>Mice, Inbred C57BL</subject><subject>Mice, Knockout</subject><subject>Mice, Transgenic</subject><subject>Pneumonia, Pneumococcal - enzymology</subject><subject>Pneumonia, Pneumococcal - genetics</subject><subject>Pneumonia, Pneumococcal - immunology</subject><subject>Streptococcus pneumoniae</subject><subject>Streptococcus pneumoniae - genetics</subject><subject>Streptococcus pneumoniae - immunology</subject><issn>0022-1767</issn><issn>1550-6606</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFUT1vFDEQtRCIXAI9FXJJwYbx916JogCRgiiAemX7ZsGRP5a1VygtvxyfcqGlmq_33ozmEfKKwaUEuX93F1LacomXjAOMQj8hO6YUDFqDfkp2AJwPzGhzRs5rvQMADVw-J2dcMAWG6R358zl4pAecgw-YGw2Z9rTEkN9SSyP61ju-pCViOs4X237-tvd0RV9-5NBCyTSVjtsidsaKtG7V49KCi0hboV_b2qvii_dbpUvGLZUcLPZN81G95Bfk2WxjxZeneEG-f7j-dvVpuP3y8ebq_e3gpYQ2OATjxGHv0BmQ3nFUvRAMZjEyOyOze2NGpyT3VnvpZsm1UubALQAb51FckDcPustafm1Y25RCPzVGm7FsdeqfY5rtlZb_h3JhFGOciw6FB6hfS60rztOyhmTX-4nBdDRpejRpOpnUKa9P6ptLePhHeHRF_AUJNZIC</recordid><startdate>20121215</startdate><enddate>20121215</enddate><creator>Endo, Yuichi</creator><creator>Takahashi, Minoru</creator><creator>Iwaki, Daisuke</creator><creator>Ishida, Yumi</creator><creator>Nakazawa, Naomi</creator><creator>Kodama, Toshihisa</creator><creator>Matsuzaka, Tomohiro</creator><creator>Kanno, Kazuko</creator><creator>Liu, Yu</creator><creator>Tsuchiya, Kohsuke</creator><creator>Kawamura, Ikuo</creator><creator>Ikawa, Masahito</creator><creator>Waguri, Satoshi</creator><creator>Wada, Ikuo</creator><creator>Matsushita, Misao</creator><creator>Schwaeble, Wilhelm J</creator><creator>Fujita, Teizo</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>7QL</scope><scope>7T5</scope><scope>C1K</scope><scope>H94</scope></search><sort><creationdate>20121215</creationdate><title>Mice deficient in ficolin, a lectin complement pathway recognition molecule, are susceptible to Streptococcus pneumoniae infection</title><author>Endo, Yuichi ; Takahashi, Minoru ; Iwaki, Daisuke ; Ishida, Yumi ; Nakazawa, Naomi ; Kodama, Toshihisa ; Matsuzaka, Tomohiro ; Kanno, Kazuko ; Liu, Yu ; Tsuchiya, Kohsuke ; Kawamura, Ikuo ; Ikawa, Masahito ; Waguri, Satoshi ; Wada, Ikuo ; Matsushita, Misao ; Schwaeble, Wilhelm J ; Fujita, Teizo</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c440t-be07b3d9beb704cb2e5d9b310f381afe1a9778b542ca6c4bf426557d2a0018f83</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>Animals</topic><topic>CHO Cells</topic><topic>Complement Activation - genetics</topic><topic>Complement Activation - immunology</topic><topic>Complement Pathway, Mannose-Binding Lectin - genetics</topic><topic>Cricetinae</topic><topic>Ficolins</topic><topic>Genetic Predisposition to Disease</topic><topic>Lectins - deficiency</topic><topic>Lectins - genetics</topic><topic>Mannose-Binding Protein-Associated Serine Proteases - deficiency</topic><topic>Mannose-Binding Protein-Associated Serine Proteases - genetics</topic><topic>Mice</topic><topic>Mice, 129 Strain</topic><topic>Mice, Inbred C57BL</topic><topic>Mice, Knockout</topic><topic>Mice, Transgenic</topic><topic>Pneumonia, Pneumococcal - enzymology</topic><topic>Pneumonia, Pneumococcal - genetics</topic><topic>Pneumonia, Pneumococcal - immunology</topic><topic>Streptococcus pneumoniae</topic><topic>Streptococcus pneumoniae - genetics</topic><topic>Streptococcus pneumoniae - immunology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Endo, Yuichi</creatorcontrib><creatorcontrib>Takahashi, Minoru</creatorcontrib><creatorcontrib>Iwaki, Daisuke</creatorcontrib><creatorcontrib>Ishida, Yumi</creatorcontrib><creatorcontrib>Nakazawa, Naomi</creatorcontrib><creatorcontrib>Kodama, Toshihisa</creatorcontrib><creatorcontrib>Matsuzaka, Tomohiro</creatorcontrib><creatorcontrib>Kanno, Kazuko</creatorcontrib><creatorcontrib>Liu, Yu</creatorcontrib><creatorcontrib>Tsuchiya, Kohsuke</creatorcontrib><creatorcontrib>Kawamura, Ikuo</creatorcontrib><creatorcontrib>Ikawa, Masahito</creatorcontrib><creatorcontrib>Waguri, Satoshi</creatorcontrib><creatorcontrib>Wada, Ikuo</creatorcontrib><creatorcontrib>Matsushita, Misao</creatorcontrib><creatorcontrib>Schwaeble, Wilhelm J</creatorcontrib><creatorcontrib>Fujita, Teizo</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>Bacteriology Abstracts (Microbiology B)</collection><collection>Immunology Abstracts</collection><collection>Environmental Sciences and Pollution Management</collection><collection>AIDS and Cancer Research Abstracts</collection><jtitle>The Journal of immunology (1950)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Endo, Yuichi</au><au>Takahashi, Minoru</au><au>Iwaki, Daisuke</au><au>Ishida, Yumi</au><au>Nakazawa, Naomi</au><au>Kodama, Toshihisa</au><au>Matsuzaka, Tomohiro</au><au>Kanno, Kazuko</au><au>Liu, Yu</au><au>Tsuchiya, Kohsuke</au><au>Kawamura, Ikuo</au><au>Ikawa, Masahito</au><au>Waguri, Satoshi</au><au>Wada, Ikuo</au><au>Matsushita, Misao</au><au>Schwaeble, Wilhelm J</au><au>Fujita, Teizo</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Mice deficient in ficolin, a lectin complement pathway recognition molecule, are susceptible to Streptococcus pneumoniae infection</atitle><jtitle>The Journal of immunology (1950)</jtitle><addtitle>J Immunol</addtitle><date>2012-12-15</date><risdate>2012</risdate><volume>189</volume><issue>12</issue><spage>5860</spage><epage>5866</epage><pages>5860-5866</pages><issn>0022-1767</issn><eissn>1550-6606</eissn><abstract>Mannose-binding lectin (MBL) and ficolin are complexed with MBL-associated serine proteases, key enzymes of complement activation via the lectin pathway, and act as soluble pattern recognition molecules in the innate immune system. Although numerous reports have revealed the importance of MBL in infectious diseases and autoimmune disorders, the role of ficolin is still unclear. To define the specific role of ficolin in vivo, we generated model mice deficient in ficolins. The ficolin A (FcnA)-deficient (Fcna(-/-)) and FcnA/ficolin B double-deficient (Fcna(-/-)b(-/-)) mice lacked FcnA-mediated complement activation in the sera, because of the absence of complexes comprising FcnA and MBL-associated serine proteases. When the host defense was evaluated by transnasal infection with a Streptococcus pneumoniae strain, which was recognized by ficolins, but not by MBLs, the survival rate was significantly reduced in all three ficolin-deficient (Fcna(-/-), Fcnb(-/-), and Fcna(-/-)b(-/-)) mice compared with wild-type mice. Reconstitution of the FcnA-mediated lectin pathway in vivo improved survival rate in Fcna(-/-) but not in Fcna(-/-)b(-/-) mice, suggesting that both FcnA and ficolin B are essential in defense against S. pneumoniae. These results suggest that ficolins play a crucial role in innate immunity against pneumococcal infection through the lectin complement pathway.</abstract><cop>United States</cop><pmid>23150716</pmid><doi>10.4049/jimmunol.1200836</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Animals CHO Cells Complement Activation - genetics Complement Activation - immunology Complement Pathway, Mannose-Binding Lectin - genetics Cricetinae Ficolins Genetic Predisposition to Disease Lectins - deficiency Lectins - genetics Mannose-Binding Protein-Associated Serine Proteases - deficiency Mannose-Binding Protein-Associated Serine Proteases - genetics Mice Mice, 129 Strain Mice, Inbred C57BL Mice, Knockout Mice, Transgenic Pneumonia, Pneumococcal - enzymology Pneumonia, Pneumococcal - genetics Pneumonia, Pneumococcal - immunology Streptococcus pneumoniae Streptococcus pneumoniae - genetics Streptococcus pneumoniae - immunology |
| title | Mice deficient in ficolin, a lectin complement pathway recognition molecule, are susceptible to Streptococcus pneumoniae infection |
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