Changes in Host Cytokine Patterns of TB Patients with Different Bacterial Loads Detected Using 16S rRNA Analysis

PLoS One. 2016 Dec 16;11(12):e0168272. doi: 10.1371/journal.pone.0168272. eCollection 2016.

Abstract

Background: Tuberculosis (TB) has overtaken HIV as the biggest infectious disease killer, with the majority of deaths occurring in sub-Saharan Africa. However it is unknown how differences in bacterial load alter host immune profiles in the sputum and blood of TB patients.

Methods: 16S ribosomal RNA analysis was used to determine bacterial load in sputum samples obtained from 173 patients with active TB (57 pre-treatment and 116 post-treatment). Host analyte concentrations in sputum and Mycobacterium tuberculosis (Mtb) antigen stimulated whole blood assay supernatants were analysed using multiplex cytokine arrays.

Results: Multiple logistic regression adjusting for age, sex and HIV status showed highly significant correlation of bacterial load with IL1β, IL2, IL1RA, IL4, IL6, IL8, IL9, IL15, IL17, EOTAX, FGF, IFN-γ, GCSF, MCP1, M1P1α, M1P1β, PDGF, TNFα, VEGF in sputum. With increasing time on treatment, FGF levels in sputum displayed the most significant inverse correlation with reduction in bacterial load.

Conclusions: We show that differences in bacterial load correlates with changes in several host biomarkers. These findings have implications for development of tests for TB diagnosis and treatment response.

MeSH terms

  • Adult
  • Africa South of the Sahara
  • Antitubercular Agents / therapeutic use
  • Bacterial Load / genetics
  • Bacterial Load / methods*
  • Cytokines / blood*
  • Female
  • Gambia
  • Humans
  • Male
  • Molecular Diagnostic Techniques
  • Mycobacterium tuberculosis / genetics*
  • RNA, Bacterial / analysis*
  • RNA, Ribosomal, 16S / analysis*
  • Sputum / microbiology
  • Treatment Outcome
  • Tuberculosis / blood*
  • Tuberculosis / diagnosis
  • Tuberculosis / drug therapy
  • Tuberculosis / microbiology*

Substances

  • Antitubercular Agents
  • Cytokines
  • RNA, Bacterial
  • RNA, Ribosomal, 16S