Follicular helper T cells promote liver pathology in mice during Schistosoma japonicum infection
Following Schistosoma japonicum (S. japonicum) infection, granulomatous responses are induced by parasite eggs trapped in host organs, particular in the liver, during the acute stage of disease. While excessive liver granulomatous responses can lead to more severe fibrosis and circulatory impairment...
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| creator | Chen, Xiaojun Yang, Xiaowei Li, Yong Zhu, Jifeng Zhou, Sha Xu, Zhipeng He, Lei Xue, Xue Zhang, Weiwei Dong, Xiaoxiao Wu, Henry Li, Carrie J Hsu, Hsiang-Ting Kong, Wenjun Liu, Feng Tripathi, Prem B Yu, Michelle S Chang, Jason Zhou, Liang Su, Chuan |
| description | Following Schistosoma japonicum (S. japonicum) infection, granulomatous responses are induced by parasite eggs trapped in host organs, particular in the liver, during the acute stage of disease. While excessive liver granulomatous responses can lead to more severe fibrosis and circulatory impairment in chronically infected host. However, the exact mechanism of hepatic granuloma formation has remained obscure. In this study, we for the first time showed that follicular helper T (Tfh) cells are recruited to the liver to upregulate hepatic granuloma formation and liver injury in S. japonicum-infected mice, and identified a novel function of macrophages in Tfh cell induction. In addition, our results showed that the generation of Tfh cells driven by macrophages is dependent on cell-cell contact and the level of inducible costimulator ligand (ICOSL) on macrophages which is regulated by CD40-CD40L signaling. Our findings uncovered a previously unappreciated role for Tfh cells in liver pathology caused by S. japonicum infection in mice. |
| doi_str_mv | 10.1371/journal.ppat.1004097 |
| format | Article |
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While excessive liver granulomatous responses can lead to more severe fibrosis and circulatory impairment in chronically infected host. However, the exact mechanism of hepatic granuloma formation has remained obscure. In this study, we for the first time showed that follicular helper T (Tfh) cells are recruited to the liver to upregulate hepatic granuloma formation and liver injury in S. japonicum-infected mice, and identified a novel function of macrophages in Tfh cell induction. In addition, our results showed that the generation of Tfh cells driven by macrophages is dependent on cell-cell contact and the level of inducible costimulator ligand (ICOSL) on macrophages which is regulated by CD40-CD40L signaling. Our findings uncovered a previously unappreciated role for Tfh cells in liver pathology caused by S. japonicum infection in mice.</description><identifier>ISSN: 1553-7374</identifier><identifier>ISSN: 1553-7366</identifier><identifier>EISSN: 1553-7374</identifier><identifier>DOI: 10.1371/journal.ppat.1004097</identifier><identifier>PMID: 24788758</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Animals ; Antigens ; B cells ; Biology and Life Sciences ; Cells, Cultured ; Eggs ; Estrone ; Experiments ; Flow cytometry ; Granuloma - immunology ; Granuloma - parasitology ; Immune system ; Inducible T-Cell Co-Stimulator Ligand - genetics ; Infections ; Liver ; Liver - immunology ; Liver - parasitology ; Liver - pathology ; Liver Diseases, Parasitic - immunology ; Liver Diseases, Parasitic - parasitology ; Lymphocytes ; Macrophages - immunology ; Macrophages - parasitology ; Macrophages - pathology ; Male ; Medicine and Health Sciences ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Pathology ; Physiological aspects ; Rodents ; Schistosoma japonicum - immunology ; Schistosoma japonicum - pathogenicity ; Schistosomiasis japonica - immunology ; Schistosomiasis japonica - pathology ; Snails - parasitology ; T cell receptors ; T cells ; T-Lymphocytes, Helper-Inducer - physiology</subject><ispartof>PLoS pathogens, 2014-05, Vol.10 (5), p.e1004097-e1004097</ispartof><rights>COPYRIGHT 2014 Public Library of Science</rights><rights>2014 Chen et al 2014 Chen et al</rights><rights>2014 Chen et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited: Chen X, Yang X, Li Y, Zhu J, Zhou S, et al. (2014) Follicular Helper T Cells Promote Liver Pathology in Mice during Schistosoma japonicum Infection. PLoS Pathog 10(5): e1004097. doi:10.1371/journal.ppat.1004097</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c633t-866d791c81430ca14912c68dc6564481693dd5fb28ea8ff7e5fa9c3651f9a9f73</citedby><cites>FETCH-LOGICAL-c633t-866d791c81430ca14912c68dc6564481693dd5fb28ea8ff7e5fa9c3651f9a9f73</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4006917/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4006917/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2096,2915,23845,27901,27902,53766,53768,79342,79343</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24788758$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Chen, Xiaojun</creatorcontrib><creatorcontrib>Yang, Xiaowei</creatorcontrib><creatorcontrib>Li, Yong</creatorcontrib><creatorcontrib>Zhu, Jifeng</creatorcontrib><creatorcontrib>Zhou, Sha</creatorcontrib><creatorcontrib>Xu, Zhipeng</creatorcontrib><creatorcontrib>He, Lei</creatorcontrib><creatorcontrib>Xue, Xue</creatorcontrib><creatorcontrib>Zhang, Weiwei</creatorcontrib><creatorcontrib>Dong, Xiaoxiao</creatorcontrib><creatorcontrib>Wu, Henry</creatorcontrib><creatorcontrib>Li, Carrie J</creatorcontrib><creatorcontrib>Hsu, Hsiang-Ting</creatorcontrib><creatorcontrib>Kong, Wenjun</creatorcontrib><creatorcontrib>Liu, Feng</creatorcontrib><creatorcontrib>Tripathi, Prem B</creatorcontrib><creatorcontrib>Yu, Michelle S</creatorcontrib><creatorcontrib>Chang, Jason</creatorcontrib><creatorcontrib>Zhou, Liang</creatorcontrib><creatorcontrib>Su, Chuan</creatorcontrib><title>Follicular helper T cells promote liver pathology in mice during Schistosoma japonicum infection</title><title>PLoS pathogens</title><addtitle>PLoS Pathog</addtitle><description>Following Schistosoma japonicum (S. japonicum) infection, granulomatous responses are induced by parasite eggs trapped in host organs, particular in the liver, during the acute stage of disease. While excessive liver granulomatous responses can lead to more severe fibrosis and circulatory impairment in chronically infected host. However, the exact mechanism of hepatic granuloma formation has remained obscure. In this study, we for the first time showed that follicular helper T (Tfh) cells are recruited to the liver to upregulate hepatic granuloma formation and liver injury in S. japonicum-infected mice, and identified a novel function of macrophages in Tfh cell induction. In addition, our results showed that the generation of Tfh cells driven by macrophages is dependent on cell-cell contact and the level of inducible costimulator ligand (ICOSL) on macrophages which is regulated by CD40-CD40L signaling. Our findings uncovered a previously unappreciated role for Tfh cells in liver pathology caused by S. japonicum infection in mice.</description><subject>Animals</subject><subject>Antigens</subject><subject>B cells</subject><subject>Biology and Life Sciences</subject><subject>Cells, Cultured</subject><subject>Eggs</subject><subject>Estrone</subject><subject>Experiments</subject><subject>Flow cytometry</subject><subject>Granuloma - immunology</subject><subject>Granuloma - parasitology</subject><subject>Immune system</subject><subject>Inducible T-Cell Co-Stimulator Ligand - genetics</subject><subject>Infections</subject><subject>Liver</subject><subject>Liver - immunology</subject><subject>Liver - parasitology</subject><subject>Liver - pathology</subject><subject>Liver Diseases, Parasitic - immunology</subject><subject>Liver Diseases, Parasitic - parasitology</subject><subject>Lymphocytes</subject><subject>Macrophages - immunology</subject><subject>Macrophages - parasitology</subject><subject>Macrophages - pathology</subject><subject>Male</subject><subject>Medicine and Health Sciences</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Mice, Knockout</subject><subject>Pathology</subject><subject>Physiological aspects</subject><subject>Rodents</subject><subject>Schistosoma japonicum - immunology</subject><subject>Schistosoma japonicum - pathogenicity</subject><subject>Schistosomiasis japonica - immunology</subject><subject>Schistosomiasis japonica - pathology</subject><subject>Snails - parasitology</subject><subject>T cell receptors</subject><subject>T cells</subject><subject>T-Lymphocytes, Helper-Inducer - physiology</subject><issn>1553-7374</issn><issn>1553-7366</issn><issn>1553-7374</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>DOA</sourceid><recordid>eNqVkl2L1DAUhoso7of-A9GCN-vFjEnz2RthWVwdWBTc9Tpm0qSTIW26Sbu4_95TZ3bZAW-k0IbT57zn5c0pijcYLTER-OM2TqnXYTkMelxihCiqxbPiGDNGFoII-vzJ-ag4yXkLDCaYvyyOKiqkFEweF78uYwjeTEGncmPDYFN5UxobQi6HFLs42jL4O6jClE0Msb0vfV923tiymZLv2_LabHweY46dLrd6iD2odQA5a0Yf-1fFC6dDtq_339Pi5-Xnm4uvi6vvX1YX51cLwwkZF5LzRtTYSEwJMhrTGleGy8ZwximVmNekaZhbV9Jq6ZywzOnaEM6wq3XtBDkt3u10hxCz2oeTFWaEIwo5ICBWO6KJequG5Dud7lXUXv0txNQqnUZvglWWWQc2mKVrQ9cNvDHMYIIQ16w5akDr037atO5sY2w_Jh0ORA__9H6j2ninKEK8xrPds71AireTzaPqfJ5z172N0-y7wqQSkleAvt-hrQZrEGwERTPj6pxIgsFXTYBa_oOCp7FwW7G3zkP9oOHDQQMwo_09tnrKWa2uf_wH--2QpTvWpJhzsu4xFYzUvLkPl6PmzVX7zYW2t08TfWx6WFXyB0mQ66w</recordid><startdate>20140501</startdate><enddate>20140501</enddate><creator>Chen, Xiaojun</creator><creator>Yang, Xiaowei</creator><creator>Li, Yong</creator><creator>Zhu, Jifeng</creator><creator>Zhou, Sha</creator><creator>Xu, Zhipeng</creator><creator>He, Lei</creator><creator>Xue, Xue</creator><creator>Zhang, Weiwei</creator><creator>Dong, Xiaoxiao</creator><creator>Wu, Henry</creator><creator>Li, Carrie J</creator><creator>Hsu, Hsiang-Ting</creator><creator>Kong, Wenjun</creator><creator>Liu, Feng</creator><creator>Tripathi, Prem B</creator><creator>Yu, Michelle S</creator><creator>Chang, Jason</creator><creator>Zhou, Liang</creator><creator>Su, Chuan</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</general><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>ISN</scope><scope>ISR</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20140501</creationdate><title>Follicular helper T cells promote liver pathology in mice during Schistosoma japonicum infection</title><author>Chen, Xiaojun ; Yang, Xiaowei ; Li, Yong ; Zhu, Jifeng ; Zhou, Sha ; Xu, Zhipeng ; He, Lei ; Xue, Xue ; Zhang, Weiwei ; Dong, Xiaoxiao ; Wu, Henry ; Li, Carrie J ; Hsu, Hsiang-Ting ; Kong, Wenjun ; Liu, Feng ; Tripathi, Prem B ; Yu, Michelle S ; Chang, Jason ; Zhou, Liang ; Su, Chuan</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c633t-866d791c81430ca14912c68dc6564481693dd5fb28ea8ff7e5fa9c3651f9a9f73</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>Animals</topic><topic>Antigens</topic><topic>B cells</topic><topic>Biology and Life Sciences</topic><topic>Cells, Cultured</topic><topic>Eggs</topic><topic>Estrone</topic><topic>Experiments</topic><topic>Flow cytometry</topic><topic>Granuloma - immunology</topic><topic>Granuloma - parasitology</topic><topic>Immune system</topic><topic>Inducible T-Cell Co-Stimulator Ligand - genetics</topic><topic>Infections</topic><topic>Liver</topic><topic>Liver - immunology</topic><topic>Liver - parasitology</topic><topic>Liver - pathology</topic><topic>Liver Diseases, Parasitic - immunology</topic><topic>Liver Diseases, Parasitic - parasitology</topic><topic>Lymphocytes</topic><topic>Macrophages - immunology</topic><topic>Macrophages - parasitology</topic><topic>Macrophages - pathology</topic><topic>Male</topic><topic>Medicine and Health Sciences</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Mice, Knockout</topic><topic>Pathology</topic><topic>Physiological aspects</topic><topic>Rodents</topic><topic>Schistosoma japonicum - immunology</topic><topic>Schistosoma japonicum - pathogenicity</topic><topic>Schistosomiasis japonica - immunology</topic><topic>Schistosomiasis japonica - pathology</topic><topic>Snails - parasitology</topic><topic>T cell receptors</topic><topic>T cells</topic><topic>T-Lymphocytes, Helper-Inducer - physiology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Chen, Xiaojun</creatorcontrib><creatorcontrib>Yang, Xiaowei</creatorcontrib><creatorcontrib>Li, Yong</creatorcontrib><creatorcontrib>Zhu, Jifeng</creatorcontrib><creatorcontrib>Zhou, Sha</creatorcontrib><creatorcontrib>Xu, Zhipeng</creatorcontrib><creatorcontrib>He, Lei</creatorcontrib><creatorcontrib>Xue, Xue</creatorcontrib><creatorcontrib>Zhang, Weiwei</creatorcontrib><creatorcontrib>Dong, Xiaoxiao</creatorcontrib><creatorcontrib>Wu, Henry</creatorcontrib><creatorcontrib>Li, Carrie J</creatorcontrib><creatorcontrib>Hsu, Hsiang-Ting</creatorcontrib><creatorcontrib>Kong, Wenjun</creatorcontrib><creatorcontrib>Liu, Feng</creatorcontrib><creatorcontrib>Tripathi, Prem B</creatorcontrib><creatorcontrib>Yu, Michelle S</creatorcontrib><creatorcontrib>Chang, Jason</creatorcontrib><creatorcontrib>Zhou, Liang</creatorcontrib><creatorcontrib>Su, Chuan</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Gale In Context: Canada</collection><collection>Gale In Context: Science</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PLoS pathogens</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Chen, Xiaojun</au><au>Yang, Xiaowei</au><au>Li, Yong</au><au>Zhu, Jifeng</au><au>Zhou, Sha</au><au>Xu, Zhipeng</au><au>He, Lei</au><au>Xue, Xue</au><au>Zhang, Weiwei</au><au>Dong, Xiaoxiao</au><au>Wu, Henry</au><au>Li, Carrie J</au><au>Hsu, Hsiang-Ting</au><au>Kong, Wenjun</au><au>Liu, Feng</au><au>Tripathi, Prem B</au><au>Yu, Michelle S</au><au>Chang, Jason</au><au>Zhou, Liang</au><au>Su, Chuan</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Follicular helper T cells promote liver pathology in mice during Schistosoma japonicum infection</atitle><jtitle>PLoS pathogens</jtitle><addtitle>PLoS Pathog</addtitle><date>2014-05-01</date><risdate>2014</risdate><volume>10</volume><issue>5</issue><spage>e1004097</spage><epage>e1004097</epage><pages>e1004097-e1004097</pages><issn>1553-7374</issn><issn>1553-7366</issn><eissn>1553-7374</eissn><abstract>Following Schistosoma japonicum (S. japonicum) infection, granulomatous responses are induced by parasite eggs trapped in host organs, particular in the liver, during the acute stage of disease. While excessive liver granulomatous responses can lead to more severe fibrosis and circulatory impairment in chronically infected host. However, the exact mechanism of hepatic granuloma formation has remained obscure. In this study, we for the first time showed that follicular helper T (Tfh) cells are recruited to the liver to upregulate hepatic granuloma formation and liver injury in S. japonicum-infected mice, and identified a novel function of macrophages in Tfh cell induction. In addition, our results showed that the generation of Tfh cells driven by macrophages is dependent on cell-cell contact and the level of inducible costimulator ligand (ICOSL) on macrophages which is regulated by CD40-CD40L signaling. Our findings uncovered a previously unappreciated role for Tfh cells in liver pathology caused by S. japonicum infection in mice.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>24788758</pmid><doi>10.1371/journal.ppat.1004097</doi><oa>free_for_read</oa></addata></record> |
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| source | Public Library of Science (PLoS) Journals Open Access; MEDLINE; DOAJ Directory of Open Access Journals; EZB-FREE-00999 freely available EZB journals; PubMed Central; PubMed Central Open Access |
| subjects | Animals Antigens B cells Biology and Life Sciences Cells, Cultured Eggs Estrone Experiments Flow cytometry Granuloma - immunology Granuloma - parasitology Immune system Inducible T-Cell Co-Stimulator Ligand - genetics Infections Liver Liver - immunology Liver - parasitology Liver - pathology Liver Diseases, Parasitic - immunology Liver Diseases, Parasitic - parasitology Lymphocytes Macrophages - immunology Macrophages - parasitology Macrophages - pathology Male Medicine and Health Sciences Mice Mice, Inbred C57BL Mice, Knockout Pathology Physiological aspects Rodents Schistosoma japonicum - immunology Schistosoma japonicum - pathogenicity Schistosomiasis japonica - immunology Schistosomiasis japonica - pathology Snails - parasitology T cell receptors T cells T-Lymphocytes, Helper-Inducer - physiology |
| title | Follicular helper T cells promote liver pathology in mice during Schistosoma japonicum infection |
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