ArticleBMC infectious diseases2019
TLR9 polymorphism correlates with immune activation, CD4 decline and plasma IP10 levels in HIV patients.
Article in BMC infectious diseases, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers, 1 of them a synthesis that pooled it.
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Who cites it
13 citing papers in PubMed, 1 synthesis or guideline pooled it, 17 citations in OpenAlex.
- Toll-like receptors polymorphisms and COVID-19: a systematic review.Molecular and cellular biochemistry · 2025Pooled it
- TLR9 gene polymorphism -1237T/C (rs5743836) is associated with low IgG antibody response against PvCSP variants in symptomatic P. vivax infections in Venezuela.PLoS neglected tropical diseases · 2025Article
- The gut virome is associated with stress-induced changes in behaviour and immune responses in mice.Nature microbiology · 2024Article
- MiR-155 Negatively Regulates Anti-Viral Innate Responses among HIV-Infected Progressors.Viruses · 2023Article
- Female Sex Hormones Upregulate the Replication Activity of HIV-1 Sub-Subtype A6 and CRF02_AG but Not HIV-1 Subtype B.Pathogens (Basel, Switzerland) · 2023Article
- Role of TLRs in HIV-1 Infection and Potential of TLR Agonists in HIV-1 Vaccine Development and Treatment Strategies.Pathogens (Basel, Switzerland) · 2023Review
- Multi-omics in HIV: searching insights to understand immunological non-response in PLHIV.Frontiers in immunology · 2023Review
- TheCells · 2021Article
- Review
- Brief Report: Toll-like Receptor 9-1635A/G Polymorphism Is Associated With HIV-1 Rebound After Four Weeks of Interruption of Antiretroviral Therapy.Journal of acquired immune deficiency syndromes (1999) · 2020Article
- Incomplete immune reconstitution in HIV/AIDS patients on antiretroviral therapy: Challenges of immunological non-responders.Journal of leukocyte biology · 2020Review
- DNA Sensing in the Innate Immune Response.Physiology (Bethesda, Md.) · 2020Review
- TLR9 and COVID-19: A Multidisciplinary Theory of a Multifaceted Therapeutic Target.Frontiers in pharmacology · 2020Article
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundThe mechanism behind HIV mediated immune activation remains debated, although the role of virus replication in this process is increasingly evident. Toll like Receptor 9 (TLR9) has been implicated in HIV mediated immune activation via sensing of viral CpG DNA. Polymorphisms in the TLR9 gene and promoter region including TLR9 1635A/G and 1486C/T have been found to be associated with multiple infectious diseases and cancers.
methodsIn the current study, we looked at the correlation of TLR9 polymorphisms 1635A/G and 1486C/T with key hallmarks of HIV disease in a cohort of 50 HIV infected patients. We analyzed CD4 counts, T cell immune activation characterized by upregulation of CD38 and HLA-DR and upregulation of plasma biomarkers of inflammation like LPS, sCD14, IL-6 and IP10 in the HIV patient cohort and compared it to healthy controls.
resultsWe found that TLR9 1635AA genotype was associated with lower CD4 counts and significantly higher immune activation in both CD4+ and CD8+ T cells. Analysis of HIV associated plasma biomarkers including LPS, sCD14, IL-6 and IP10 revealed a strong correlation between IP10 and immune activation. Interestingly, IP10 levels were also found to be higher in HIV patients with the 1635AA genotype. Furthermore, the TLR9 1486C/T polymorphism that is in linkage disequilibrium with 1635A/G was weakly associated with lower CD4 counts, higher CD8 immune activation and higher IP10 levels.
conclusionsAs TLR9 stimulation is known to induce IP10 production by dendritic cells, our findings provide new insights into HIV mediated immune activation and CD4 loss. TLR9 stimulation by viral CpG DNA may be important to HIV immunopathogenesis and the TLR9 polymorphisms 1635A/G and 1486C/T may be associated with disease progression.
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