Hyperglycaemia is inversely correlated with live M. bovis BCG-specific CD4+ T cell responses in Tanzanian adults with latent or active tuberculosis

Abstract

Introduction: The rising prevalence of Diabetes mellitus (DM) in high TB-endemic countries may adversely affect sustainability of TB control since DM constitutes a risk factor for development of active tuberculosis (TB). The impact of DM on TB specific adaptive immune responses remains poorly addressed, particularly in people living in Sub-Saharan countries. We performed a functional characterization of TB specific cellular immune response in Tanzanian subjects with active or latent Mycobacterium tuberculosis (Mtb) infection stratified by their diabetic status. Methods: HIV negative active TB patients (≥18 years) with Xpert MTB/RIF positive pulmonary TB were included before starting TB treatment in Dar es Salaam, Tanzania between April and December 2013. HIV negative healthy controls latently infected with TB but without past TB history were also included. Active and latent TB patients were stratified in two groups according to their diabetic status. Peripheral Blood Mononuclear cells were stimulated with either live M. bovis BCG or Mtb-specific peptide pools and analyzed by intracellular cytokine staining and polychromatic flow cytometry. Results: Our results show a lower frequency of IFN-γ CD4+ T cells in patients with active TB and DM compared to patients with active TB only after live M. bovis BCG (p = 0.04) but not after Mtb peptide pools re-stimulation. Irrespective of TB status, level of glycaemia is selectively inversely correlated with IFN-γ and TNF-α CD4+ T cell production (p = 0.02 and p = 0.03) after live M. bovis BCG stimulation. Conclusions: These results support the hypothesis that hyperglycaemia negatively impacts antigen processing and/or presentation of whole mycobacteria delaying secretion of key cytokines involved in TB immunity.