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.
Hum Genomics
; 13(1): 59, 2019 11 28.
Article
en En
| MEDLINE
| ID: mdl-31779701
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.Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Estrés Psicológico
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Fumar
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Infecciones por VIH
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Interferones
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Perfilación de la Expresión Génica
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Terapia Antirretroviral Altamente Activa
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Depresión
Tipo de estudio:
Clinical_trials
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Diagnostic_studies
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Observational_studies
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Prognostic_studies
/
Risk_factors_studies
Límite:
Adult
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Aged
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Hum Genomics
Asunto de la revista:
GENETICA
Año:
2019
Tipo del documento:
Article
País de afiliación:
Estados Unidos