Transcriptomic analysis of monocytes from HIV-positive men on antiretroviral therapy reveals effects of tobacco smoking on interferon and stress response systems associated with depressive symptoms
Abstract Background Tobacco smoking induces immunomodulatory and pro-inflammatory effects associated with transcriptome changes in monocytes and other immune cell types. While smoking is prevalent in HIV-infected (HIV+) individuals, few studies have investigated its effects on gene expression in thi...
| Main Authors: | , , |
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| Format: | Article |
| Language: | English |
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BMC
2019-11-01
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| Series: | Human Genomics |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s40246-019-0247-x |
| _version_ | 1811300676509106176 |
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| author | David R. Lorenz Vikas Misra Dana Gabuzda |
| author_facet | David R. Lorenz Vikas Misra Dana Gabuzda |
| author_sort | David R. Lorenz |
| collection | DOAJ |
| description | Abstract Background Tobacco smoking induces immunomodulatory and pro-inflammatory effects associated with transcriptome changes in monocytes and other immune cell types. While smoking is prevalent in HIV-infected (HIV+) individuals, few studies have investigated its effects on gene expression in this population. Here, we report whole-transcriptome analyses of 125 peripheral blood monocyte samples from ART-treated HIV+ and uninfected (HIV−) men enrolled in the Multicenter AIDS Cohort Study (MACS) (n = 25 HIV+ smokers, n = 60 HIV+ non-smokers, n = 40 HIV− non-smoking controls). Gene expression profiling was performed using Illumina HumanHT-12 Expression BeadChip microarrays. Differential expression analysis was performed with weighted linear regression models using the R limma package, followed by functional enrichment and Ingenuity Pathway analyses. Results A total of 286 genes were differentially expressed in monocytes from HIV+ smokers compared with HIV− non-smokers; upregulated genes (n = 180) were enriched for immune and interferon response, chemical/stress response, mitochondria, and extracellular vesicle gene ontology (GO) terms. Expression of genes related to immune/interferon responses (AIM2, FCGR1A-B, IFI16, SP100), stress/chemical responses (APAF1, HSPD1, KLF4), and mitochondrial function (CISD1, MTHFD2, SQOR) was upregulated in HIV+ non-smokers and further increased in HIV+ smokers. Gene expression changes associated with smoking in previous studies of human monocytes were also observed (SASH1, STAB1, PID1, MMP25). Depressive symptoms (CES-D scores ≥ 16) were more prevalent in HIV+ tobacco smokers compared with HIV+ and HIV− non-smokers (50% vs. 26% and 13%, respectively; p = 0.007), and upregulation of immune/interferon response genes, including IFI35, IFNAR1, OAS1-2, STAT1, and SP100, was associated with depressive symptoms in logistic regression models adjusted for HIV status and smoking (p < 0.05). Network models linked the Stat1-mediated interferon pathway to transcriptional regulator Klf4 and smoking-associated toll-like receptor scaffolding protein Sash1, suggesting inter-relationships between smoking-associated genes, control of monocyte differentiation, and interferon-mediated inflammatory responses. Conclusions This study characterizes immune, interferon, stress response, and mitochondrial-associated gene expression changes in monocytes from HIV+ tobacco smokers, and identifies augmented interferon and stress responses associated with depressive symptoms. These findings help to explain complex interrelationships between pro-inflammatory effects of HIV and smoking, and their combined impact on comorbidities prevalent in HIV+ individuals. |
| first_indexed | 2024-04-13T06:54:50Z |
| format | Article |
| id | doaj.art-2af5ab0ad716429697e0c714d54f99d1 |
| institution | Directory Open Access Journal |
| issn | 1479-7364 |
| language | English |
| last_indexed | 2024-04-13T06:54:50Z |
| publishDate | 2019-11-01 |
| publisher | BMC |
| record_format | Article |
| series | Human Genomics |
| spelling | doaj.art-2af5ab0ad716429697e0c714d54f99d12022-12-22T02:57:17ZengBMCHuman Genomics1479-73642019-11-0113111510.1186/s40246-019-0247-xTranscriptomic analysis of monocytes from HIV-positive men on antiretroviral therapy reveals effects of tobacco smoking on interferon and stress response systems associated with depressive symptomsDavid R. Lorenz0Vikas Misra1Dana Gabuzda2Department of Cancer Immunology and Virology, Dana-Farber Cancer InstituteDepartment of Cancer Immunology and Virology, Dana-Farber Cancer InstituteDepartment of Cancer Immunology and Virology, Dana-Farber Cancer InstituteAbstract Background Tobacco smoking induces immunomodulatory and pro-inflammatory effects associated with transcriptome changes in monocytes and other immune cell types. While smoking is prevalent in HIV-infected (HIV+) individuals, few studies have investigated its effects on gene expression in this population. Here, we report whole-transcriptome analyses of 125 peripheral blood monocyte samples from ART-treated HIV+ and uninfected (HIV−) men enrolled in the Multicenter AIDS Cohort Study (MACS) (n = 25 HIV+ smokers, n = 60 HIV+ non-smokers, n = 40 HIV− non-smoking controls). Gene expression profiling was performed using Illumina HumanHT-12 Expression BeadChip microarrays. Differential expression analysis was performed with weighted linear regression models using the R limma package, followed by functional enrichment and Ingenuity Pathway analyses. Results A total of 286 genes were differentially expressed in monocytes from HIV+ smokers compared with HIV− non-smokers; upregulated genes (n = 180) were enriched for immune and interferon response, chemical/stress response, mitochondria, and extracellular vesicle gene ontology (GO) terms. Expression of genes related to immune/interferon responses (AIM2, FCGR1A-B, IFI16, SP100), stress/chemical responses (APAF1, HSPD1, KLF4), and mitochondrial function (CISD1, MTHFD2, SQOR) was upregulated in HIV+ non-smokers and further increased in HIV+ smokers. Gene expression changes associated with smoking in previous studies of human monocytes were also observed (SASH1, STAB1, PID1, MMP25). Depressive symptoms (CES-D scores ≥ 16) were more prevalent in HIV+ tobacco smokers compared with HIV+ and HIV− non-smokers (50% vs. 26% and 13%, respectively; p = 0.007), and upregulation of immune/interferon response genes, including IFI35, IFNAR1, OAS1-2, STAT1, and SP100, was associated with depressive symptoms in logistic regression models adjusted for HIV status and smoking (p < 0.05). Network models linked the Stat1-mediated interferon pathway to transcriptional regulator Klf4 and smoking-associated toll-like receptor scaffolding protein Sash1, suggesting inter-relationships between smoking-associated genes, control of monocyte differentiation, and interferon-mediated inflammatory responses. Conclusions This study characterizes immune, interferon, stress response, and mitochondrial-associated gene expression changes in monocytes from HIV+ tobacco smokers, and identifies augmented interferon and stress responses associated with depressive symptoms. These findings help to explain complex interrelationships between pro-inflammatory effects of HIV and smoking, and their combined impact on comorbidities prevalent in HIV+ individuals.https://doi.org/10.1186/s40246-019-0247-xHIVTobaccoSmokingTranscriptomicsMonocytesImmune response |
| spellingShingle | David R. Lorenz Vikas Misra Dana Gabuzda Transcriptomic analysis of monocytes from HIV-positive men on antiretroviral therapy reveals effects of tobacco smoking on interferon and stress response systems associated with depressive symptoms Human Genomics HIV Tobacco Smoking Transcriptomics Monocytes Immune response |
| title | Transcriptomic analysis of monocytes from HIV-positive men on antiretroviral therapy reveals effects of tobacco smoking on interferon and stress response systems associated with depressive symptoms |
| title_full | Transcriptomic analysis of monocytes from HIV-positive men on antiretroviral therapy reveals effects of tobacco smoking on interferon and stress response systems associated with depressive symptoms |
| title_fullStr | Transcriptomic analysis of monocytes from HIV-positive men on antiretroviral therapy reveals effects of tobacco smoking on interferon and stress response systems associated with depressive symptoms |
| title_full_unstemmed | Transcriptomic analysis of monocytes from HIV-positive men on antiretroviral therapy reveals effects of tobacco smoking on interferon and stress response systems associated with depressive symptoms |
| title_short | Transcriptomic analysis of monocytes from HIV-positive men on antiretroviral therapy reveals effects of tobacco smoking on interferon and stress response systems associated with depressive symptoms |
| title_sort | transcriptomic analysis of monocytes from hiv positive men on antiretroviral therapy reveals effects of tobacco smoking on interferon and stress response systems associated with depressive symptoms |
| topic | HIV Tobacco Smoking Transcriptomics Monocytes Immune response |
| url | https://doi.org/10.1186/s40246-019-0247-x |
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