Chronic hyperglycemia drives alterations in macrophage effector function in pulmonary tuberculosis.

Area of Science:

• Immunology
• Infectious Diseases
• Endocrinology

Background:

• Diabetes mellitus (DM) is increasingly prevalent in tuberculosis (TB) endemic regions.
• Hyperglycemia associated with DM may influence TB susceptibility and progression.
• The impact of hyperglycemia on macrophage-mediated innate immunity against TB is not well understood.

Purpose of the Study:

• To investigate the effects of uncontrolled DM and hyperglycemia on macrophage effector functions in TB patients.
• To assess how these immune alterations correlate with TB disease severity.

Main Methods:

• Macrophage phagocytic capacity against BCG was measured.
• Surface expression of pattern recognition receptors (PRRs) including CD11b, CD14, CD206, MARCO, and TLR-2 was analyzed using flow cytometry.
• Reactive oxygen species (ROS) and nitric oxide (NO) production were quantified.

Main Results:

• Patients with uncontrolled DM and TB (PTB+DM) exhibited dysregulated macrophage phagocytosis and altered PRR expression (CD11b, MARCO, CD206).
• These changes were linked to reduced phagocytic capacity.
• PTB+DM patients showed higher ROS and lower NO levels, correlating with increased disease severity.

Conclusions:

• Uncontrolled hyperglycemia in DM significantly impairs macrophage functions crucial for combating TB infection.
• Altered PRR expression and effector molecule production contribute to TB susceptibility and progression in diabetic individuals.
• These findings highlight the detrimental role of hyperglycemia in the interplay between DM and TB.