Antiretroviral Treatment-Induced Decrease in Immune Activation Contributes to Reduced Susceptibility to Tuberculosis...

Area of Science:

• Immunology
• Infectious Diseases
• Molecular Biology

Background:

• HIV-1 and tuberculosis (TB) coinfection poses significant health risks.
• Antiretroviral treatment (ART) is known to reduce active TB incidence in coinfected individuals.
• Understanding host immune responses during ART in the context of Mycobacterium tuberculosis (Mtb) sensitization is crucial.

Purpose of the Study:

• To investigate host immune responses during the initial 6 months of ART in HIV-1/Mtb coinfected individuals with latent TB.
• To analyze changes in gene expression and soluble immune mediators associated with ART initiation.

Main Methods:

• RNA sequencing (RNAseq) of whole blood to analyze gene expression profiles.
• Measurement of 65 soluble analytes in plasma.
• Analysis of 30 soluble analytes in QuantiFERON Gold (QFT) samples, including IL-1alpha, IL-1beta, MCP-1, and IP-10.

Main Results:

• Significant decrease in RNA abundance for Hallmark IFN-alpha, IFN-gamma, IL-6/JAK/STAT3 signaling, and inflammatory response pathway genes at 6 months of ART.
• Reduced levels of inflammatory markers in plasma after 6 months of ART.
• Decreased IL-1alpha, IL-1beta, and MCP-1 concentrations, with a significant increase in IP-10 (Ag-nil) and CD4 T cell counts expressing chemokine receptors.

Conclusions:

• ART initiation leads to decreased immune activation and inflammation in HIV-1/Mtb coinfected individuals.
• ART enhances antigen responsiveness, indicated by increased IP-10 levels and CD4 T cell populations.
• ART-induced immune modulation may contribute to the reduced susceptibility to active tuberculosis in coinfected persons.