Transcriptome profiling of gene expression during immunisation trial against Fasciola hepatica: identification of genes and pathways involved in conferring immunoprotection in a murine model
Fasciolosis remains a significant food-borne trematode disease causing high morbidity around the world and affecting grazing animals and humans. A deeper understanding concerning the molecular mechanisms by which Fasciola hepatica infection occurs, as well as the molecular basis involved in acquirin...
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description | Fasciolosis remains a significant food-borne trematode disease causing high morbidity around the world and affecting grazing animals and humans. A deeper understanding concerning the molecular mechanisms by which Fasciola hepatica infection occurs, as well as the molecular basis involved in acquiring protection is extremely important when designing and selecting new vaccine candidates. The present study provides a first report of microarray-based technology for describing changes in the splenic gene expression profile for mice immunised with a highly effective, protection-inducing, multi-epitope, subunit-based, chemically-synthesised vaccine candidate against F. hepatica.
The mice were immunised with synthetic peptides containing B- and T-cell epitopes, which are derived from F. hepatica cathepsin B and amoebapore proteins, as novel vaccine candidates against F. hepatica formulated in an adjuvant adaptation vaccination system; they were experimentally challenged with F. hepatica metacercariae. Spleen RNA from mice immunised with the highest protection-inducing synthetic peptides was isolated, amplified and labelled using Affymetrix standardised protocols. Data was then background corrected, normalised and the expression signal was calculated. The Ingenuity Pathway Analysis tool was then used for analysing differentially expressed gene identifiers for annotating bio-functions and constructing and visualising molecular interaction networks.
Mice immunised with a combination of three peptides containing T-cell epitopes induced high protection against experimental challenge according to survival rates and hepatic damage scores. It also induced differential expression of 820 genes, 168 genes being up-regulated and 652 genes being down-regulated, p value |
doi_str_mv | 10.1186/s12879-017-2205-3 |
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The mice were immunised with synthetic peptides containing B- and T-cell epitopes, which are derived from F. hepatica cathepsin B and amoebapore proteins, as novel vaccine candidates against F. hepatica formulated in an adjuvant adaptation vaccination system; they were experimentally challenged with F. hepatica metacercariae. Spleen RNA from mice immunised with the highest protection-inducing synthetic peptides was isolated, amplified and labelled using Affymetrix standardised protocols. Data was then background corrected, normalised and the expression signal was calculated. The Ingenuity Pathway Analysis tool was then used for analysing differentially expressed gene identifiers for annotating bio-functions and constructing and visualising molecular interaction networks.
Mice immunised with a combination of three peptides containing T-cell epitopes induced high protection against experimental challenge according to survival rates and hepatic damage scores. It also induced differential expression of 820 genes, 168 genes being up-regulated and 652 genes being down-regulated, p value <0.05, fold change ranging from -2.944 to 7.632. A functional study of these genes revealed changes in the pathways related to nitric oxide and reactive oxygen species production, Interleukin-12 signalling and production in macrophages and Interleukin-8 signalling with up-regulation of S100 calcium-binding protein A8, Matrix metallopeptidase 9 and CXC chemokine receptor 2 genes.
The data obtained in the present study provided us with a more comprehensive overview concerning the possible molecular pathways implied in inducing protection against F. hepatica in a murine model, which could be useful for evaluating future vaccine candidates.</description><identifier>ISSN: 1471-2334</identifier><identifier>EISSN: 1471-2334</identifier><identifier>DOI: 10.1186/s12879-017-2205-3</identifier><identifier>PMID: 28114888</identifier><language>eng</language><publisher>England: BioMed Central Ltd</publisher><subject>Amino acids ; Animals ; Antibodies, Helminth - immunology ; Antigens ; Calgranulin A - drug effects ; Calgranulin A - genetics ; Care and treatment ; Development and progression ; Disease ; Epitopes - immunology ; Fasciola hepatica - immunology ; Fascioliasis - prevention & control ; Female ; Fluke infections ; Gene expression ; Gene Expression - drug effects ; Gene Expression Profiling ; Genetic aspects ; Health aspects ; Immune response ; Infections ; Interleukin-12 - genetics ; Interleukin-8 - drug effects ; Interleukin-8 - genetics ; Laboratory animals ; Matrix Metalloproteinase 9 - drug effects ; Matrix Metalloproteinase 9 - genetics ; Mice ; Parasites ; Peptides ; Peptides - immunology ; Proteins ; Protozoan Vaccines - pharmacology ; Receptors, Interleukin-8B - drug effects ; Receptors, Interleukin-8B - genetics ; RNA, Messenger - drug effects ; RNA, Messenger - metabolism ; Spleen - drug effects ; Spleen - metabolism ; Testing ; Up-Regulation ; Vaccination ; Vaccines</subject><ispartof>BMC infectious diseases, 2017-01, Vol.17 (1), p.94-94, Article 94</ispartof><rights>COPYRIGHT 2017 BioMed Central Ltd.</rights><rights>Copyright BioMed Central 2017</rights><rights>The Author(s). 2017</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c562t-e6e7ce3aa8a8932043c0a75f8d2dbd211c7c120c720cb3123eb4f7cdd7cf5d073</citedby><cites>FETCH-LOGICAL-c562t-e6e7ce3aa8a8932043c0a75f8d2dbd211c7c120c720cb3123eb4f7cdd7cf5d073</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/PMC5259852/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5259852/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,27901,27902,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28114888$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Rojas-Caraballo, Jose</creatorcontrib><creatorcontrib>López-Abán, Julio</creatorcontrib><creatorcontrib>Moreno-Pérez, Darwin Andrés</creatorcontrib><creatorcontrib>Vicente, Belén</creatorcontrib><creatorcontrib>Fernández-Soto, Pedro</creatorcontrib><creatorcontrib>Del Olmo, Esther</creatorcontrib><creatorcontrib>Patarroyo, Manuel Alfonso</creatorcontrib><creatorcontrib>Muro, Antonio</creatorcontrib><title>Transcriptome profiling of gene expression during immunisation trial against Fasciola hepatica: identification of genes and pathways involved in conferring immunoprotection in a murine model</title><title>BMC infectious diseases</title><addtitle>BMC Infect Dis</addtitle><description>Fasciolosis remains a significant food-borne trematode disease causing high morbidity around the world and affecting grazing animals and humans. A deeper understanding concerning the molecular mechanisms by which Fasciola hepatica infection occurs, as well as the molecular basis involved in acquiring protection is extremely important when designing and selecting new vaccine candidates. The present study provides a first report of microarray-based technology for describing changes in the splenic gene expression profile for mice immunised with a highly effective, protection-inducing, multi-epitope, subunit-based, chemically-synthesised vaccine candidate against F. hepatica.
The mice were immunised with synthetic peptides containing B- and T-cell epitopes, which are derived from F. hepatica cathepsin B and amoebapore proteins, as novel vaccine candidates against F. hepatica formulated in an adjuvant adaptation vaccination system; they were experimentally challenged with F. hepatica metacercariae. Spleen RNA from mice immunised with the highest protection-inducing synthetic peptides was isolated, amplified and labelled using Affymetrix standardised protocols. Data was then background corrected, normalised and the expression signal was calculated. The Ingenuity Pathway Analysis tool was then used for analysing differentially expressed gene identifiers for annotating bio-functions and constructing and visualising molecular interaction networks.
Mice immunised with a combination of three peptides containing T-cell epitopes induced high protection against experimental challenge according to survival rates and hepatic damage scores. It also induced differential expression of 820 genes, 168 genes being up-regulated and 652 genes being down-regulated, p value <0.05, fold change ranging from -2.944 to 7.632. A functional study of these genes revealed changes in the pathways related to nitric oxide and reactive oxygen species production, Interleukin-12 signalling and production in macrophages and Interleukin-8 signalling with up-regulation of S100 calcium-binding protein A8, Matrix metallopeptidase 9 and CXC chemokine receptor 2 genes.
The data obtained in the present study provided us with a more comprehensive overview concerning the possible molecular pathways implied in inducing protection against F. hepatica in a murine model, which could be useful for evaluating future vaccine candidates.</description><subject>Amino acids</subject><subject>Animals</subject><subject>Antibodies, Helminth - immunology</subject><subject>Antigens</subject><subject>Calgranulin A - drug effects</subject><subject>Calgranulin A - genetics</subject><subject>Care and treatment</subject><subject>Development and progression</subject><subject>Disease</subject><subject>Epitopes - immunology</subject><subject>Fasciola hepatica - immunology</subject><subject>Fascioliasis - prevention & control</subject><subject>Female</subject><subject>Fluke infections</subject><subject>Gene expression</subject><subject>Gene Expression - drug effects</subject><subject>Gene Expression Profiling</subject><subject>Genetic aspects</subject><subject>Health aspects</subject><subject>Immune response</subject><subject>Infections</subject><subject>Interleukin-12 - genetics</subject><subject>Interleukin-8 - drug effects</subject><subject>Interleukin-8 - genetics</subject><subject>Laboratory animals</subject><subject>Matrix Metalloproteinase 9 - drug effects</subject><subject>Matrix Metalloproteinase 9 - genetics</subject><subject>Mice</subject><subject>Parasites</subject><subject>Peptides</subject><subject>Peptides - immunology</subject><subject>Proteins</subject><subject>Protozoan Vaccines - pharmacology</subject><subject>Receptors, Interleukin-8B - drug effects</subject><subject>Receptors, Interleukin-8B - genetics</subject><subject>RNA, Messenger - drug effects</subject><subject>RNA, Messenger - metabolism</subject><subject>Spleen - drug effects</subject><subject>Spleen - metabolism</subject><subject>Testing</subject><subject>Up-Regulation</subject><subject>Vaccination</subject><subject>Vaccines</subject><issn>1471-2334</issn><issn>1471-2334</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNqNks9u1DAQxiMEoqXwAFyQJS5wSPGfZO3lUKmqKFSqVAkKV2vWnqSuEnuxk6V9OZ4NZ3cpu4gDsiKPMr_vG3s8RfGS0WPG1OxdYlzJeUmZLDmndSkeFYeskqzkQlSPd-KD4llKtzSDis-fFgdcMVYppQ6Ln9cRfDLRLYfQI1nG0LjO-ZaEhrTokeDdMmJKLnhixzhlXN-P3iUYpn9DdNARaMH5NJBzSMaFDsgNLnPewHviLPrBNTle81vbRMBbkpmbH3CfiPOr0K3Q5oCY4BuMfyqFfKYBzVqd00D66RhI-mCxe148aaBL-GK7HxVfzz9cn30qL68-XpydXpamnvGhxBlKgwJAgZoLTithKMi6UZbbheWMGWkYp0bmbyEYF7ioGmmslaapLZXiqDjZ-C7HRY_W5DtF6PQyuh7ivQ7g9H7GuxvdhpWueT1XNc8Gb7YGMXwfMQ26d8lg14HHMCadn5PNKJ-va73-C70NY_T5ehMlJKWq3qFa6FA734Rc10ym-rRSdEZrJifq-B9UXhZ7lzuN-bVxX_B2T5CZAe-GFsaU9MWXz__PXn3bZ9mGNTGkFLF56B2jehpmvRlmnWdUT8OsRda82m36g-L39Ipfl77zqQ</recordid><startdate>20170123</startdate><enddate>20170123</enddate><creator>Rojas-Caraballo, Jose</creator><creator>López-Abán, Julio</creator><creator>Moreno-Pérez, Darwin Andrés</creator><creator>Vicente, Belén</creator><creator>Fernández-Soto, Pedro</creator><creator>Del Olmo, Esther</creator><creator>Patarroyo, Manuel Alfonso</creator><creator>Muro, Antonio</creator><general>BioMed Central Ltd</general><general>BioMed Central</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>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7QL</scope><scope>7T2</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8C1</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>C1K</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>H94</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20170123</creationdate><title>Transcriptome profiling of gene expression during immunisation trial against Fasciola hepatica: identification of genes and pathways involved in conferring immunoprotection in a murine model</title><author>Rojas-Caraballo, Jose ; López-Abán, Julio ; Moreno-Pérez, Darwin Andrés ; Vicente, Belén ; Fernández-Soto, Pedro ; Del Olmo, Esther ; Patarroyo, Manuel Alfonso ; Muro, Antonio</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c562t-e6e7ce3aa8a8932043c0a75f8d2dbd211c7c120c720cb3123eb4f7cdd7cf5d073</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Amino acids</topic><topic>Animals</topic><topic>Antibodies, Helminth - immunology</topic><topic>Antigens</topic><topic>Calgranulin A - drug effects</topic><topic>Calgranulin A - genetics</topic><topic>Care and treatment</topic><topic>Development and progression</topic><topic>Disease</topic><topic>Epitopes - immunology</topic><topic>Fasciola hepatica - immunology</topic><topic>Fascioliasis - prevention & control</topic><topic>Female</topic><topic>Fluke infections</topic><topic>Gene expression</topic><topic>Gene Expression - drug effects</topic><topic>Gene Expression Profiling</topic><topic>Genetic aspects</topic><topic>Health aspects</topic><topic>Immune response</topic><topic>Infections</topic><topic>Interleukin-12 - genetics</topic><topic>Interleukin-8 - drug effects</topic><topic>Interleukin-8 - genetics</topic><topic>Laboratory animals</topic><topic>Matrix Metalloproteinase 9 - drug effects</topic><topic>Matrix Metalloproteinase 9 - genetics</topic><topic>Mice</topic><topic>Parasites</topic><topic>Peptides</topic><topic>Peptides - immunology</topic><topic>Proteins</topic><topic>Protozoan Vaccines - pharmacology</topic><topic>Receptors, Interleukin-8B - drug effects</topic><topic>Receptors, Interleukin-8B - genetics</topic><topic>RNA, Messenger - drug effects</topic><topic>RNA, Messenger - metabolism</topic><topic>Spleen - drug effects</topic><topic>Spleen - metabolism</topic><topic>Testing</topic><topic>Up-Regulation</topic><topic>Vaccination</topic><topic>Vaccines</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Rojas-Caraballo, Jose</creatorcontrib><creatorcontrib>López-Abán, Julio</creatorcontrib><creatorcontrib>Moreno-Pérez, Darwin Andrés</creatorcontrib><creatorcontrib>Vicente, Belén</creatorcontrib><creatorcontrib>Fernández-Soto, Pedro</creatorcontrib><creatorcontrib>Del Olmo, Esther</creatorcontrib><creatorcontrib>Patarroyo, Manuel Alfonso</creatorcontrib><creatorcontrib>Muro, Antonio</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: Opposing Viewpoints</collection><collection>Gale In Context: Science</collection><collection>ProQuest Central (Corporate)</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Health and Safety Science Abstracts (Full archive)</collection><collection>Virology and AIDS Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Public Health Database</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>ProQuest Central</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>BMC infectious diseases</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Rojas-Caraballo, Jose</au><au>López-Abán, Julio</au><au>Moreno-Pérez, Darwin Andrés</au><au>Vicente, Belén</au><au>Fernández-Soto, Pedro</au><au>Del Olmo, Esther</au><au>Patarroyo, Manuel Alfonso</au><au>Muro, Antonio</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Transcriptome profiling of gene expression during immunisation trial against Fasciola hepatica: identification of genes and pathways involved in conferring immunoprotection in a murine model</atitle><jtitle>BMC infectious diseases</jtitle><addtitle>BMC Infect Dis</addtitle><date>2017-01-23</date><risdate>2017</risdate><volume>17</volume><issue>1</issue><spage>94</spage><epage>94</epage><pages>94-94</pages><artnum>94</artnum><issn>1471-2334</issn><eissn>1471-2334</eissn><abstract>Fasciolosis remains a significant food-borne trematode disease causing high morbidity around the world and affecting grazing animals and humans. A deeper understanding concerning the molecular mechanisms by which Fasciola hepatica infection occurs, as well as the molecular basis involved in acquiring protection is extremely important when designing and selecting new vaccine candidates. The present study provides a first report of microarray-based technology for describing changes in the splenic gene expression profile for mice immunised with a highly effective, protection-inducing, multi-epitope, subunit-based, chemically-synthesised vaccine candidate against F. hepatica.
The mice were immunised with synthetic peptides containing B- and T-cell epitopes, which are derived from F. hepatica cathepsin B and amoebapore proteins, as novel vaccine candidates against F. hepatica formulated in an adjuvant adaptation vaccination system; they were experimentally challenged with F. hepatica metacercariae. Spleen RNA from mice immunised with the highest protection-inducing synthetic peptides was isolated, amplified and labelled using Affymetrix standardised protocols. Data was then background corrected, normalised and the expression signal was calculated. The Ingenuity Pathway Analysis tool was then used for analysing differentially expressed gene identifiers for annotating bio-functions and constructing and visualising molecular interaction networks.
Mice immunised with a combination of three peptides containing T-cell epitopes induced high protection against experimental challenge according to survival rates and hepatic damage scores. It also induced differential expression of 820 genes, 168 genes being up-regulated and 652 genes being down-regulated, p value <0.05, fold change ranging from -2.944 to 7.632. A functional study of these genes revealed changes in the pathways related to nitric oxide and reactive oxygen species production, Interleukin-12 signalling and production in macrophages and Interleukin-8 signalling with up-regulation of S100 calcium-binding protein A8, Matrix metallopeptidase 9 and CXC chemokine receptor 2 genes.
The data obtained in the present study provided us with a more comprehensive overview concerning the possible molecular pathways implied in inducing protection against F. hepatica in a murine model, which could be useful for evaluating future vaccine candidates.</abstract><cop>England</cop><pub>BioMed Central Ltd</pub><pmid>28114888</pmid><doi>10.1186/s12879-017-2205-3</doi><tpages>1</tpages><oa>free_for_read</oa></addata></record> |
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subjects | Amino acids Animals Antibodies, Helminth - immunology Antigens Calgranulin A - drug effects Calgranulin A - genetics Care and treatment Development and progression Disease Epitopes - immunology Fasciola hepatica - immunology Fascioliasis - prevention & control Female Fluke infections Gene expression Gene Expression - drug effects Gene Expression Profiling Genetic aspects Health aspects Immune response Infections Interleukin-12 - genetics Interleukin-8 - drug effects Interleukin-8 - genetics Laboratory animals Matrix Metalloproteinase 9 - drug effects Matrix Metalloproteinase 9 - genetics Mice Parasites Peptides Peptides - immunology Proteins Protozoan Vaccines - pharmacology Receptors, Interleukin-8B - drug effects Receptors, Interleukin-8B - genetics RNA, Messenger - drug effects RNA, Messenger - metabolism Spleen - drug effects Spleen - metabolism Testing Up-Regulation Vaccination Vaccines |
title | Transcriptome profiling of gene expression during immunisation trial against Fasciola hepatica: identification of genes and pathways involved in conferring immunoprotection in a murine model |
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