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BMC Infectious Diseases
Published in: BMC Infectious Diseases 1/2019

Open Access 01-12-2019 | Human Immunodeficiency Virus | Research article

TLR9 polymorphism correlates with immune activation, CD4 decline and plasma IP10 levels in HIV patients

Authors: Anjali Joshi, Erin B. Punke, Tugba Mehmetoglu-Gurbuz, Diego P. Peralta, Himanshu Garg

Published in: BMC Infectious Diseases | Issue 1/2019

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Abstract

Background

The 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.

Methods

In 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.

Results

We 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.

Conclusions

As 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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Metadata
Title
TLR9 polymorphism correlates with immune activation, CD4 decline and plasma IP10 levels in HIV patients
Authors
Anjali Joshi
Erin B. Punke
Tugba Mehmetoglu-Gurbuz
Diego P. Peralta
Himanshu Garg
Publication date
01-12-2019
Publisher
BioMed Central
Published in
BMC Infectious Diseases / Issue 1/2019
Electronic ISSN: 1471-2334
DOI
https://doi.org/10.1186/s12879-019-3697-9

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