Chronic hyperglycemia drives alterations in macrophage effector function in pulmonary tuberculosis

Abstract

Diabetes mellitus (DM) alters immune responses and given the rising prevalence of DM in tuberculosis (TB) endemic countries; hyperglycemia can be a potential risk factor for active TB development. However, the impact of hyperglycemia on TB‐specific innate immune response in terms of macrophage functions remains poorly addressed. We assessed macrophage effector functions in uncontrolled DM patients with or without TB infection (PTB+DM and DM), non‐diabetic TB patients (PTB), and non‐diabetic‐uninfected controls. Phagocytic capacity against BCG and surface expression of different pattern recognition receptors (PRRs) (CD11b, CD14, CD206, MARCO, and TLR‐2) were measured via flow cytometry. Effector molecules (ROS and NO) required for bacterial killing were assessed via DCFDA and Griess reaction respectively. A systematic dysregulation in phagocytic capacity with concurrent alterations in the expression pattern of key PRRs (CD11b, MARCO, and CD206) was observed in PTB+DM. These altered PRR expressions were associated with decreased phagocytic capacity of macrophages. Similarly, ROS was aberrantly higher while NO was lower in PTB+DM. These altered macrophage functions were positively correlated with increasing disease severity. Our results highlight several key patterns of immune dysregulation against TB infection under hyperglycemic conditions and highlight a negative impact of hyperglycemia with etiology and progression of TB.

Chronic Insulin Resistance and Changes of M1/M2 Polarization in Macrophages Due to Abnormal Tyrosines

“…assessed macrophage effector functions in uncontrolled DM patients with or without tuberculosis (TB) infection (TB+DM and DM), non-diabetic TB patients, and non-diabeticuninfected controls. In their study they found, among others, reduced phagocytic capacity of macrophages, reduced NO levels (indicating reduced iNOS activation) and increased CD206 (M2 macrophage marker) levels in macrophages under diabetic conditions [37].…”

Pulmonary tuberculosis and diabetes mellitus: Epidemiology, pathogenesis and therapeutic management (Review)

“…An increased susceptibility to PTB occurs due to a delayed innate immune response to the alveolar macrophages in Mycobacterium tuberculosis infection in DM ( 17 ). A recent study found that hyperglycemia affected the phagocytosis ability of macrophages by the change of the expression pattern of recognition receptors in PTB ( 18 ). In anti-tuberculosis immunity, the phagocytosis ability of alveolar macrophages is significantly decreased when human alveolar macrophages are directly exposed to hyperglycemia ( 19 ).…”