Cytokine and chemokine expression profiles in response to Mycobacterium tuberculosis stimulation are altered in HIV-infected compared to HIV-uninfected subjects with active tuberculosis

Tuberculosis (Edinb). 2015 Sep;95(5):555-61. doi: 10.1016/j.tube.2015.05.001. Epub 2015 May 22.

Abstract

Mycobacterium tuberculosis (Mtb) infects nearly 2 million people annually and is the most common cause of death in HIV-infected individuals. Tuberculosis (TB) diagnostics cater to HIV-uninfected individuals in non-endemic countries, are expensive, slow, and lack sensitivity for those most affected. Patterns of soluble immune markers from Mtb-stimulated immune cells are not well defined in HIV co-infection. We assessed immune differences between HIV-infected and HIV-uninfected individuals with active TB utilizing IFNγ-based QuantiFERON®-TB Gold In-Tube (QFT) testing in Nairobi, Kenya. Excess QFT supernatants were used to measure cytokine and chemokine responses by a 17-plex bead array. Mtb/HIV co-infected participants were significantly less likely to be QFT+ (47.2% versus 84.2% in the HIV-uninfected group), and demonstrated lower expression of all cytokines except for IFNα2. Receiver operator characteristic analyses identified IL-1α as a potential marker of co-infection. Among HIV-infected individuals, CD4+ T cell count correlated weakly with the expression of several analytes. Co-expression analysis highlighted differences in immune profiles between the groups. These data suggest that there is a unique and detectable Mtb-specific immune response in co-infection. A better understanding of Mtb immunology can translate into much needed immunodiagnostics with enhanced sensitivity in HIV-infected individuals, facilitating their opportunity to obtain live-saving treatment.

Keywords: Chemokine; Co-infection; Cytokine; HIV; Interferon gamma release assay; ROC curve analysis; Tuberculosis.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Area Under Curve
  • Biomarkers / blood
  • Chemokines / blood*
  • Coinfection*
  • Cytokines / blood*
  • Female
  • HIV Infections / blood*
  • HIV Infections / diagnosis
  • HIV Infections / immunology
  • HIV Infections / virology
  • Host-Pathogen Interactions
  • Humans
  • Interferon-gamma / blood
  • Interferon-gamma Release Tests
  • Kenya
  • Male
  • Middle Aged
  • Mycobacterium tuberculosis / immunology*
  • Mycobacterium tuberculosis / pathogenicity
  • Predictive Value of Tests
  • ROC Curve
  • Tuberculosis, Pulmonary / blood*
  • Tuberculosis, Pulmonary / diagnosis
  • Tuberculosis, Pulmonary / immunology
  • Tuberculosis, Pulmonary / microbiology

Substances

  • Biomarkers
  • Chemokines
  • Cytokines
  • IFNG protein, human
  • Interferon-gamma