Adequate Th2-type response associates with restricted bacterial growth in latent mycobacterial infection of zebrafish
Tuberculosis is still a major health problem worldwide. Currently it is not known what kind of immune responses lead to successful control and clearance of Mycobacterium tuberculosis. This gap in knowledge is reflected by the inability to develop sufficient diagnostic and therapeutic tools to fight...
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| Veröffentlicht in: | PLoS pathogens 2014-06, Vol.10 (6), p.e1004190-e1004190 |
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| creator | Hammarén, Milka Marjut Oksanen, Kaisa Ester Nisula, Hanna Maria Luukinen, Bruno Vincent Pesu, Marko Rämet, Mika Parikka, Mataleena |
| description | Tuberculosis is still a major health problem worldwide. Currently it is not known what kind of immune responses lead to successful control and clearance of Mycobacterium tuberculosis. This gap in knowledge is reflected by the inability to develop sufficient diagnostic and therapeutic tools to fight tuberculosis. We have used the Mycobacterium marinum infection model in the adult zebrafish and taken advantage of heterogeneity of zebrafish population to dissect the characteristics of adaptive immune responses, some of which are associated with well-controlled latency or bacterial clearance while others with progressive infection. Differences in T cell responses between subpopulations were measured at the transcriptional level. It was discovered that a high total T cell level was usually associated with lower bacterial loads alongside with a T helper 2 (Th2)-type gene expression signature. At late time points, spontaneous reactivation with apparent symptoms was characterized by a low Th2/Th1 marker ratio and a substantial induction of foxp3 reflecting the level of regulatory T cells. Characteristic gata3/tbx21 has potential as a biomarker for the status of mycobacterial disease. |
| doi_str_mv | 10.1371/journal.ppat.1004190 |
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Currently it is not known what kind of immune responses lead to successful control and clearance of Mycobacterium tuberculosis. This gap in knowledge is reflected by the inability to develop sufficient diagnostic and therapeutic tools to fight tuberculosis. We have used the Mycobacterium marinum infection model in the adult zebrafish and taken advantage of heterogeneity of zebrafish population to dissect the characteristics of adaptive immune responses, some of which are associated with well-controlled latency or bacterial clearance while others with progressive infection. Differences in T cell responses between subpopulations were measured at the transcriptional level. It was discovered that a high total T cell level was usually associated with lower bacterial loads alongside with a T helper 2 (Th2)-type gene expression signature. At late time points, spontaneous reactivation with apparent symptoms was characterized by a low Th2/Th1 marker ratio and a substantial induction of foxp3 reflecting the level of regulatory T cells. Characteristic gata3/tbx21 has potential as a biomarker for the status of mycobacterial disease.</description><identifier>ISSN: 1553-7374</identifier><identifier>ISSN: 1553-7366</identifier><identifier>EISSN: 1553-7374</identifier><identifier>DOI: 10.1371/journal.ppat.1004190</identifier><identifier>PMID: 24968056</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Adaptive Immunity ; Algorithms ; Analysis ; Animals ; Animals, Genetically Modified ; Antibiotics ; Bacterial Load ; Biology and Life Sciences ; Biomarkers - blood ; Biomarkers - metabolism ; Colleges & universities ; Confidence intervals ; Diagnosis ; Disease Models, Animal ; Disease Progression ; Diseases ; Distribution ; Forkhead Transcription Factors - blood ; Forkhead Transcription Factors - genetics ; Forkhead Transcription Factors - metabolism ; GATA3 Transcription Factor - blood ; GATA3 Transcription Factor - genetics ; GATA3 Transcription Factor - metabolism ; Gene expression ; Gene Expression Regulation ; Health aspects ; Immune system ; Infections ; Lymphocyte Count ; Lymphocytes ; Lymphopoiesis ; Medicine and Health Sciences ; Microbial Viability ; Mutation ; Mycobacterium Infections, Nontuberculous - blood ; Mycobacterium Infections, Nontuberculous - immunology ; Mycobacterium Infections, Nontuberculous - metabolism ; Mycobacterium Infections, Nontuberculous - microbiology ; Mycobacterium marinum - growth & development ; Mycobacterium marinum - immunology ; Mycobacterium marinum - isolation & purification ; Physiological aspects ; Population ; T cells ; T-Box Domain Proteins - blood ; T-Box Domain Proteins - genetics ; T-Box Domain Proteins - metabolism ; Th1 Cells - immunology ; Th1 Cells - metabolism ; Th1 Cells - microbiology ; Th1 Cells - pathology ; Th2 Cells - immunology ; Th2 Cells - metabolism ; Th2 Cells - microbiology ; Th2 Cells - pathology ; Tuberculosis ; Up-Regulation ; Vaccines ; Zebra fish ; Zebrafish - genetics ; Zebrafish - immunology ; Zebrafish - metabolism ; Zebrafish - microbiology ; Zebrafish Proteins - blood ; Zebrafish Proteins - genetics ; Zebrafish Proteins - metabolism</subject><ispartof>PLoS pathogens, 2014-06, Vol.10 (6), p.e1004190-e1004190</ispartof><rights>COPYRIGHT 2014 Public Library of Science</rights><rights>2014 Hammarén et al 2014 Hammarén et al</rights><rights>2014 Hammarén 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: Hammarén MM, Oksanen KE, Nisula HM, Luukinen BV, Pesu M, et al. (2014) Adequate Th2-Type Response Associates with Restricted Bacterial Growth in Latent Mycobacterial Infection of Zebrafish. PLoS Pathog 10(6): e1004190. doi:10.1371/journal.ppat.1004190</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c633t-8422a135e75a919d4924768e0a4b7a8c97ac600761cd329d59f5b840aec21bb13</citedby><cites>FETCH-LOGICAL-c633t-8422a135e75a919d4924768e0a4b7a8c97ac600761cd329d59f5b840aec21bb13</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/PMC4072801/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4072801/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,2100,2926,23865,27923,27924,53790,53792,79371,79372</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24968056$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Ramakrishnan, Lalita</contributor><creatorcontrib>Hammarén, Milka Marjut</creatorcontrib><creatorcontrib>Oksanen, Kaisa Ester</creatorcontrib><creatorcontrib>Nisula, Hanna Maria</creatorcontrib><creatorcontrib>Luukinen, Bruno Vincent</creatorcontrib><creatorcontrib>Pesu, Marko</creatorcontrib><creatorcontrib>Rämet, Mika</creatorcontrib><creatorcontrib>Parikka, Mataleena</creatorcontrib><title>Adequate Th2-type response associates with restricted bacterial growth in latent mycobacterial infection of zebrafish</title><title>PLoS pathogens</title><addtitle>PLoS Pathog</addtitle><description>Tuberculosis is still a major health problem worldwide. Currently it is not known what kind of immune responses lead to successful control and clearance of Mycobacterium tuberculosis. This gap in knowledge is reflected by the inability to develop sufficient diagnostic and therapeutic tools to fight tuberculosis. We have used the Mycobacterium marinum infection model in the adult zebrafish and taken advantage of heterogeneity of zebrafish population to dissect the characteristics of adaptive immune responses, some of which are associated with well-controlled latency or bacterial clearance while others with progressive infection. Differences in T cell responses between subpopulations were measured at the transcriptional level. It was discovered that a high total T cell level was usually associated with lower bacterial loads alongside with a T helper 2 (Th2)-type gene expression signature. At late time points, spontaneous reactivation with apparent symptoms was characterized by a low Th2/Th1 marker ratio and a substantial induction of foxp3 reflecting the level of regulatory T cells. Characteristic gata3/tbx21 has potential as a biomarker for the status of mycobacterial disease.</description><subject>Adaptive Immunity</subject><subject>Algorithms</subject><subject>Analysis</subject><subject>Animals</subject><subject>Animals, Genetically Modified</subject><subject>Antibiotics</subject><subject>Bacterial Load</subject><subject>Biology and Life Sciences</subject><subject>Biomarkers - blood</subject><subject>Biomarkers - metabolism</subject><subject>Colleges & universities</subject><subject>Confidence intervals</subject><subject>Diagnosis</subject><subject>Disease Models, Animal</subject><subject>Disease Progression</subject><subject>Diseases</subject><subject>Distribution</subject><subject>Forkhead Transcription Factors - blood</subject><subject>Forkhead Transcription Factors - genetics</subject><subject>Forkhead Transcription Factors - metabolism</subject><subject>GATA3 Transcription Factor - blood</subject><subject>GATA3 Transcription Factor - genetics</subject><subject>GATA3 Transcription Factor - metabolism</subject><subject>Gene expression</subject><subject>Gene Expression Regulation</subject><subject>Health aspects</subject><subject>Immune system</subject><subject>Infections</subject><subject>Lymphocyte Count</subject><subject>Lymphocytes</subject><subject>Lymphopoiesis</subject><subject>Medicine and Health Sciences</subject><subject>Microbial Viability</subject><subject>Mutation</subject><subject>Mycobacterium Infections, Nontuberculous - blood</subject><subject>Mycobacterium Infections, Nontuberculous - immunology</subject><subject>Mycobacterium Infections, Nontuberculous - metabolism</subject><subject>Mycobacterium Infections, Nontuberculous - microbiology</subject><subject>Mycobacterium marinum - growth & development</subject><subject>Mycobacterium marinum - immunology</subject><subject>Mycobacterium marinum - isolation & purification</subject><subject>Physiological aspects</subject><subject>Population</subject><subject>T cells</subject><subject>T-Box Domain Proteins - blood</subject><subject>T-Box Domain Proteins - genetics</subject><subject>T-Box Domain Proteins - metabolism</subject><subject>Th1 Cells - immunology</subject><subject>Th1 Cells - metabolism</subject><subject>Th1 Cells - microbiology</subject><subject>Th1 Cells - pathology</subject><subject>Th2 Cells - immunology</subject><subject>Th2 Cells - metabolism</subject><subject>Th2 Cells - microbiology</subject><subject>Th2 Cells - pathology</subject><subject>Tuberculosis</subject><subject>Up-Regulation</subject><subject>Vaccines</subject><subject>Zebra fish</subject><subject>Zebrafish - genetics</subject><subject>Zebrafish - immunology</subject><subject>Zebrafish - metabolism</subject><subject>Zebrafish - microbiology</subject><subject>Zebrafish Proteins - blood</subject><subject>Zebrafish Proteins - genetics</subject><subject>Zebrafish Proteins - metabolism</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>eNqVkktv1DAUhSMEoqXwDxBEYgOLGez4FW8qjSoeI1UgQVlbN46T8SgTp7ZDGX49TmdaGokN8sKWz3ePr45vlr3EaImJwO-3bvQ9dMthgLjECFEs0aPsFDNGFoII-vjB-SR7FsJ2YgjmT7OTgkpeIsZPs3FVm-sRosmvNsUi7geTexMG1weTQwhO26SF_MbGzSREb3U0dV5B2ryFLm-9u0ma7fMukX3Md3vt_sq2b4yO1vW5a_LfpvLQ2LB5nj1poAvmxXE_y358_HB18Xlx-fXT-mJ1udCckLgoaVEAJswIBhLLmsqCCl4aBLQSUGopQHOEBMe6JoWsmWxYVVIERhe4qjA5y14ffIfOBXVMLCjMqGCiYHQi1geidrBVg7c78HvlwKrbC-dbBT5a3RlVaaFRZZgoa06lRCB4eoxiRDjGWMvkdX58bax2ptYpDQ_dzHSu9HajWvdTUSSKEk3NvD0aeHc9prTVzgZtug5648bbvtPXU8ZpQt8c0BZSaylllxz1hKsVKQvJkuXU0fIfVFq12VntetPYdD8reDcrSEw0v2ILYwhq_f3bf7Bf5iw9sNq7ELxp7lPBSE3jfPc5ahpndRznVPbqYaL3RXfzS_4A0e_yBg</recordid><startdate>20140601</startdate><enddate>20140601</enddate><creator>Hammarén, Milka Marjut</creator><creator>Oksanen, Kaisa Ester</creator><creator>Nisula, Hanna Maria</creator><creator>Luukinen, Bruno Vincent</creator><creator>Pesu, Marko</creator><creator>Rämet, Mika</creator><creator>Parikka, Mataleena</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>20140601</creationdate><title>Adequate Th2-type response associates with restricted bacterial growth in latent mycobacterial infection of zebrafish</title><author>Hammarén, Milka Marjut ; 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Currently it is not known what kind of immune responses lead to successful control and clearance of Mycobacterium tuberculosis. This gap in knowledge is reflected by the inability to develop sufficient diagnostic and therapeutic tools to fight tuberculosis. We have used the Mycobacterium marinum infection model in the adult zebrafish and taken advantage of heterogeneity of zebrafish population to dissect the characteristics of adaptive immune responses, some of which are associated with well-controlled latency or bacterial clearance while others with progressive infection. Differences in T cell responses between subpopulations were measured at the transcriptional level. It was discovered that a high total T cell level was usually associated with lower bacterial loads alongside with a T helper 2 (Th2)-type gene expression signature. At late time points, spontaneous reactivation with apparent symptoms was characterized by a low Th2/Th1 marker ratio and a substantial induction of foxp3 reflecting the level of regulatory T cells. Characteristic gata3/tbx21 has potential as a biomarker for the status of mycobacterial disease.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>24968056</pmid><doi>10.1371/journal.ppat.1004190</doi><oa>free_for_read</oa></addata></record> |
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| subjects | Adaptive Immunity Algorithms Analysis Animals Animals, Genetically Modified Antibiotics Bacterial Load Biology and Life Sciences Biomarkers - blood Biomarkers - metabolism Colleges & universities Confidence intervals Diagnosis Disease Models, Animal Disease Progression Diseases Distribution Forkhead Transcription Factors - blood Forkhead Transcription Factors - genetics Forkhead Transcription Factors - metabolism GATA3 Transcription Factor - blood GATA3 Transcription Factor - genetics GATA3 Transcription Factor - metabolism Gene expression Gene Expression Regulation Health aspects Immune system Infections Lymphocyte Count Lymphocytes Lymphopoiesis Medicine and Health Sciences Microbial Viability Mutation Mycobacterium Infections, Nontuberculous - blood Mycobacterium Infections, Nontuberculous - immunology Mycobacterium Infections, Nontuberculous - metabolism Mycobacterium Infections, Nontuberculous - microbiology Mycobacterium marinum - growth & development Mycobacterium marinum - immunology Mycobacterium marinum - isolation & purification Physiological aspects Population T cells T-Box Domain Proteins - blood T-Box Domain Proteins - genetics T-Box Domain Proteins - metabolism Th1 Cells - immunology Th1 Cells - metabolism Th1 Cells - microbiology Th1 Cells - pathology Th2 Cells - immunology Th2 Cells - metabolism Th2 Cells - microbiology Th2 Cells - pathology Tuberculosis Up-Regulation Vaccines Zebra fish Zebrafish - genetics Zebrafish - immunology Zebrafish - metabolism Zebrafish - microbiology Zebrafish Proteins - blood Zebrafish Proteins - genetics Zebrafish Proteins - metabolism |
| title | Adequate Th2-type response associates with restricted bacterial growth in latent mycobacterial infection of zebrafish |
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