The effect of antiretroviral treatment on selected genes in whole blood from HIV-infected adults sensitised by Mycobacterium tuberculosis
HIV-1 co-infection is a leading cause of susceptibility to tuberculosis (TB), with the risk of TB being increased at all stages of HIV-1 infection. Antiretroviral treatment (ART) is the most effective way to reduce the risk of TB in HIV-1 co-infected people. Studying protective, ART-induced, immune...
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| description | HIV-1 co-infection is a leading cause of susceptibility to tuberculosis (TB), with the risk of TB being increased at all stages of HIV-1 infection. Antiretroviral treatment (ART) is the most effective way to reduce the risk of TB in HIV-1 co-infected people. Studying protective, ART-induced, immune restoration in HIV-1 infected individuals sensitised by Mycobacterium tuberculosis (Mtb) can thus help identify mechanisms of protection against TB. In order to understand ART-mediated prevention of TB in HIV-1 infected adults, we investigated the expression of 30 genes in whole blood from HIV-1 infected patients during the first 6 months of ART-induced immune reconstitution. The 30 selected genes were previously described to be differentially expressed between sorted Mtb specific central and effector memory CD4 T cells. HIV-1 infected persons sensitised by Mtb were recruited in Khayelitsha, South Africa, when initiating ART. RNA was extracted from whole blood at initiation and 1, 3 and 6 months of ART. qRT-PCR was used to determine gene expression and three reference 'housekeeping' genes were used to calculate the fold change in the expression of each gene relative to day 0 of ART. Results were assessed longitudinally. We observed a decrease in the expression of a number of genes at 6 months of ART, reflecting a decrease in immune activation. However, following correction for multiple comparisons and increasing CD4 counts, only the decrease in CD27 gene expression remained statistically significant. While not statistically significant, a number of genes also showed increased expression at various timepoints, illustrating the broad regeneration of the T cell pool in HIV-1 infected adults on ART. Our findings generate hypotheses underlying ART- induced protective immune reconstitution and may pave the way for future studies to evaluate ART mediated prevention of TB in HIV-1 infected persons. |
| doi_str_mv | 10.1371/journal.pone.0209516 |
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Antiretroviral treatment (ART) is the most effective way to reduce the risk of TB in HIV-1 co-infected people. Studying protective, ART-induced, immune restoration in HIV-1 infected individuals sensitised by Mycobacterium tuberculosis (Mtb) can thus help identify mechanisms of protection against TB. In order to understand ART-mediated prevention of TB in HIV-1 infected adults, we investigated the expression of 30 genes in whole blood from HIV-1 infected patients during the first 6 months of ART-induced immune reconstitution. The 30 selected genes were previously described to be differentially expressed between sorted Mtb specific central and effector memory CD4 T cells. HIV-1 infected persons sensitised by Mtb were recruited in Khayelitsha, South Africa, when initiating ART. RNA was extracted from whole blood at initiation and 1, 3 and 6 months of ART. qRT-PCR was used to determine gene expression and three reference 'housekeeping' genes were used to calculate the fold change in the expression of each gene relative to day 0 of ART. Results were assessed longitudinally. We observed a decrease in the expression of a number of genes at 6 months of ART, reflecting a decrease in immune activation. However, following correction for multiple comparisons and increasing CD4 counts, only the decrease in CD27 gene expression remained statistically significant. While not statistically significant, a number of genes also showed increased expression at various timepoints, illustrating the broad regeneration of the T cell pool in HIV-1 infected adults on ART. Our findings generate hypotheses underlying ART- induced protective immune reconstitution and may pave the way for future studies to evaluate ART mediated prevention of TB in HIV-1 infected persons.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0209516</identifier><identifier>PMID: 30589870</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Adults ; Analysis ; Antiretroviral agents ; Antiretroviral drugs ; Antiretroviral therapy ; Antiretroviral Therapy, Highly Active ; Biology and Life Sciences ; Blood ; CD27 antigen ; CD4 antigen ; CD4 Lymphocyte Count ; CD4-Positive T-Lymphocytes - immunology ; CD4-Positive T-Lymphocytes - metabolism ; CD4-Positive T-Lymphocytes - virology ; Coinfection ; Crick, Francis ; Dosage and administration ; Drug therapy ; Effector cells ; Female ; Gene expression ; Gene Expression Profiling ; Gene Expression Regulation - drug effects ; Genes ; Genetic aspects ; Genotype & phenotype ; Health risks ; HIV ; HIV infections ; HIV Infections - drug therapy ; HIV Infections - genetics ; HIV Infections - immunology ; HIV Infections - virology ; HIV-1 - physiology ; Human immunodeficiency virus ; Humans ; Immune reconstitution ; Immunization ; Immunological memory ; Infections ; Infectious diseases ; Interferon-gamma Release Tests ; Lymphocytes ; Lymphocytes T ; Male ; Medicine ; Medicine and health sciences ; Memory cells ; Mycobacterium tuberculosis ; Mycobacterium tuberculosis - immunology ; Prevention ; Regeneration ; Restoration ; Ribonucleic acid ; Risk factors ; Risk reduction ; RNA ; Statistical analysis ; Statistical significance ; Treatment Outcome ; Tuberculosis ; Tuberculosis - immunology ; Tuberculosis - metabolism ; Tuberculosis - microbiology ; Viral Load</subject><ispartof>PloS one, 2018-12, Vol.13 (12), p.e0209516</ispartof><rights>COPYRIGHT 2018 Public Library of Science</rights><rights>2018 Jhilmeet et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2018 Jhilmeet et al 2018 Jhilmeet et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c585t-1093be0bbd5e61b0b8f51c714a2ea32f3b5e911b3b69c18bd306c8a485e2485c3</citedby><cites>FETCH-LOGICAL-c585t-1093be0bbd5e61b0b8f51c714a2ea32f3b5e911b3b69c18bd306c8a485e2485c3</cites><orcidid>0000-0001-6102-2375 ; 0000-0002-7086-2621 ; 0000-0002-9796-2040</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6307796/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6307796/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2096,2915,23845,27901,27902,53766,53768,79569,79570</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30589870$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Jhilmeet, Nishtha</creatorcontrib><creatorcontrib>Lowe, David M</creatorcontrib><creatorcontrib>Riou, Catherine</creatorcontrib><creatorcontrib>Scriba, Thomas J</creatorcontrib><creatorcontrib>Coussens, Anna</creatorcontrib><creatorcontrib>Goliath, Rene</creatorcontrib><creatorcontrib>Wilkinson, Robert J</creatorcontrib><creatorcontrib>Wilkinson, Katalin Andrea</creatorcontrib><title>The effect of antiretroviral treatment on selected genes in whole blood from HIV-infected adults sensitised by Mycobacterium tuberculosis</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>HIV-1 co-infection is a leading cause of susceptibility to tuberculosis (TB), with the risk of TB being increased at all stages of HIV-1 infection. Antiretroviral treatment (ART) is the most effective way to reduce the risk of TB in HIV-1 co-infected people. Studying protective, ART-induced, immune restoration in HIV-1 infected individuals sensitised by Mycobacterium tuberculosis (Mtb) can thus help identify mechanisms of protection against TB. In order to understand ART-mediated prevention of TB in HIV-1 infected adults, we investigated the expression of 30 genes in whole blood from HIV-1 infected patients during the first 6 months of ART-induced immune reconstitution. The 30 selected genes were previously described to be differentially expressed between sorted Mtb specific central and effector memory CD4 T cells. HIV-1 infected persons sensitised by Mtb were recruited in Khayelitsha, South Africa, when initiating ART. RNA was extracted from whole blood at initiation and 1, 3 and 6 months of ART. qRT-PCR was used to determine gene expression and three reference 'housekeeping' genes were used to calculate the fold change in the expression of each gene relative to day 0 of ART. Results were assessed longitudinally. We observed a decrease in the expression of a number of genes at 6 months of ART, reflecting a decrease in immune activation. However, following correction for multiple comparisons and increasing CD4 counts, only the decrease in CD27 gene expression remained statistically significant. While not statistically significant, a number of genes also showed increased expression at various timepoints, illustrating the broad regeneration of the T cell pool in HIV-1 infected adults on ART. Our findings generate hypotheses underlying ART- induced protective immune reconstitution and may pave the way for future studies to evaluate ART mediated prevention of TB in HIV-1 infected persons.</description><subject>Adults</subject><subject>Analysis</subject><subject>Antiretroviral agents</subject><subject>Antiretroviral drugs</subject><subject>Antiretroviral therapy</subject><subject>Antiretroviral Therapy, Highly Active</subject><subject>Biology and Life Sciences</subject><subject>Blood</subject><subject>CD27 antigen</subject><subject>CD4 antigen</subject><subject>CD4 Lymphocyte Count</subject><subject>CD4-Positive T-Lymphocytes - immunology</subject><subject>CD4-Positive T-Lymphocytes - metabolism</subject><subject>CD4-Positive T-Lymphocytes - virology</subject><subject>Coinfection</subject><subject>Crick, Francis</subject><subject>Dosage and administration</subject><subject>Drug therapy</subject><subject>Effector cells</subject><subject>Female</subject><subject>Gene expression</subject><subject>Gene Expression Profiling</subject><subject>Gene Expression Regulation - drug effects</subject><subject>Genes</subject><subject>Genetic aspects</subject><subject>Genotype & phenotype</subject><subject>Health risks</subject><subject>HIV</subject><subject>HIV infections</subject><subject>HIV Infections - drug therapy</subject><subject>HIV Infections - genetics</subject><subject>HIV Infections - immunology</subject><subject>HIV Infections - virology</subject><subject>HIV-1 - physiology</subject><subject>Human immunodeficiency virus</subject><subject>Humans</subject><subject>Immune reconstitution</subject><subject>Immunization</subject><subject>Immunological memory</subject><subject>Infections</subject><subject>Infectious diseases</subject><subject>Interferon-gamma Release Tests</subject><subject>Lymphocytes</subject><subject>Lymphocytes T</subject><subject>Male</subject><subject>Medicine</subject><subject>Medicine and health sciences</subject><subject>Memory cells</subject><subject>Mycobacterium tuberculosis</subject><subject>Mycobacterium tuberculosis - immunology</subject><subject>Prevention</subject><subject>Regeneration</subject><subject>Restoration</subject><subject>Ribonucleic acid</subject><subject>Risk factors</subject><subject>Risk reduction</subject><subject>RNA</subject><subject>Statistical analysis</subject><subject>Statistical significance</subject><subject>Treatment Outcome</subject><subject>Tuberculosis</subject><subject>Tuberculosis - 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Antiretroviral treatment (ART) is the most effective way to reduce the risk of TB in HIV-1 co-infected people. Studying protective, ART-induced, immune restoration in HIV-1 infected individuals sensitised by Mycobacterium tuberculosis (Mtb) can thus help identify mechanisms of protection against TB. In order to understand ART-mediated prevention of TB in HIV-1 infected adults, we investigated the expression of 30 genes in whole blood from HIV-1 infected patients during the first 6 months of ART-induced immune reconstitution. The 30 selected genes were previously described to be differentially expressed between sorted Mtb specific central and effector memory CD4 T cells. HIV-1 infected persons sensitised by Mtb were recruited in Khayelitsha, South Africa, when initiating ART. RNA was extracted from whole blood at initiation and 1, 3 and 6 months of ART. qRT-PCR was used to determine gene expression and three reference 'housekeeping' genes were used to calculate the fold change in the expression of each gene relative to day 0 of ART. Results were assessed longitudinally. We observed a decrease in the expression of a number of genes at 6 months of ART, reflecting a decrease in immune activation. However, following correction for multiple comparisons and increasing CD4 counts, only the decrease in CD27 gene expression remained statistically significant. While not statistically significant, a number of genes also showed increased expression at various timepoints, illustrating the broad regeneration of the T cell pool in HIV-1 infected adults on ART. Our findings generate hypotheses underlying ART- induced protective immune reconstitution and may pave the way for future studies to evaluate ART mediated prevention of TB in HIV-1 infected persons.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>30589870</pmid><doi>10.1371/journal.pone.0209516</doi><orcidid>https://orcid.org/0000-0001-6102-2375</orcidid><orcidid>https://orcid.org/0000-0002-7086-2621</orcidid><orcidid>https://orcid.org/0000-0002-9796-2040</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2018-12, Vol.13 (12), p.e0209516 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_2161061370 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central; Free Full-Text Journals in Chemistry; Public Library of Science (PLoS) |
| subjects | Adults Analysis Antiretroviral agents Antiretroviral drugs Antiretroviral therapy Antiretroviral Therapy, Highly Active Biology and Life Sciences Blood CD27 antigen CD4 antigen CD4 Lymphocyte Count CD4-Positive T-Lymphocytes - immunology CD4-Positive T-Lymphocytes - metabolism CD4-Positive T-Lymphocytes - virology Coinfection Crick, Francis Dosage and administration Drug therapy Effector cells Female Gene expression Gene Expression Profiling Gene Expression Regulation - drug effects Genes Genetic aspects Genotype & phenotype Health risks HIV HIV infections HIV Infections - drug therapy HIV Infections - genetics HIV Infections - immunology HIV Infections - virology HIV-1 - physiology Human immunodeficiency virus Humans Immune reconstitution Immunization Immunological memory Infections Infectious diseases Interferon-gamma Release Tests Lymphocytes Lymphocytes T Male Medicine Medicine and health sciences Memory cells Mycobacterium tuberculosis Mycobacterium tuberculosis - immunology Prevention Regeneration Restoration Ribonucleic acid Risk factors Risk reduction RNA Statistical analysis Statistical significance Treatment Outcome Tuberculosis Tuberculosis - immunology Tuberculosis - metabolism Tuberculosis - microbiology Viral Load |
| title | The effect of antiretroviral treatment on selected genes in whole blood from HIV-infected adults sensitised by Mycobacterium tuberculosis |
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