Chronic hyperglycemia impairs anti-microbial function of macrophages in response to Mycobacterium tuberculosis infection

Gaurav Kumar Chaubey, Radheshyam Modanwal, Rahul Dilawari, Sharmila Talukdar, Asmita Dhiman, Surbhi Chaudhary, Anil Patidar, Chaaya Iyengar Raje, Manoj Raje

Research output: Contribution to journalArticlepeer-review

Abstract

Diabetes mellitus (DM) is a major risk factor for tuberculosis (TB), though the underlying mechanisms linking DM and TB remain ambiguous. Macrophages are a key player in the innate immune response and their phagocytic ability is enhanced in response to microbial infections. Upon infection or inflammation, they also repel invading pathogens by generating; reactive oxygen species (ROS), reactive nitrogen species (RNS), pro-inflammatory cytokines (IL-1β and IL-6), and anti-inflammatory cytokines (IL-10). However, the robustness of these innate defensive capabilities of macrophages when exposed to hyperglycemia remains unclear. In our current work, we explored the production of these host defense molecules in response to challenge with Mycobacterium tuberculosis (Mtb) infection and lipopolysaccharide (LPS) stimulation. Utilizing peritoneal macrophages from high-fat diet + streptozotocin induced diabetic mice and hyperglycemic THP-1-derived macrophages as model systems; we found that LPS stimulation and Mtb infection were ineffective in stimulating the production of ROS, RNS, and pro-inflammatory cytokines in cells exposed to hyperglycemia. On the contrary, an increase in production of anti-inflammatory cytokines was observed. To confirm the mechanism of decreased anti-bacterial activity of the diabetic macrophage, we explored activation status of these compromised macrophages and found decreased surface expression of activation (TLR-4) and differentiation markers (CD11b and CD11c). We postulate that this could be the cause for higher susceptibility for Mtb infection among diabetic individuals.

Original languageEnglish (US)
JournalImmunologic Research
DOIs
StateAccepted/In press - 2024
Externally publishedYes

Keywords

  • Anti-inflammatory cytokines
  • Diabetes
  • Mycobacterium tuberculosis
  • Pro-inflammatory cytokines
  • ROS/RNS
  • Tuberculosis

ASJC Scopus subject areas

  • Immunology

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