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Glycaemic burden disrupts innate immunity in TB by modulating CD206 expression and macrophage antimicrobial responses.

Alisha Arora·Sudhasini Panda·Kalpana Luthra·Anant Mohan·Yashdeep Gupta·Umesh Kumar·Archana Singh
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Abstract

Tuberculosis (TB) and diabetes mellitus (DM) represent a growing dual global health burden, with chronic hyperglycaemia recognized as a major modifier of host immunity against Mycobacterium tuberculosis (Mtb). Macrophages, central to pathogen recognition, phagocytosis, antigen presentation, and intracellular killing, may be particularly vulnerable to diabetic metabolic dysregulation. This study evaluated phenotypic and functional macrophage alterations in individuals with pulmonary TB, type 2 DM, TB-DM comorbidity, and healthy controls. Surface receptor expression was analysed by multicolour flow cytometry, while phagocytosis and intracellular bacterial clearance were assessed using FITC-labelled Mtb assays and colony-forming unit enumeration. Hyperglycaemia was associated with reduced CD11b, MARCO, and TLR2 expression alongside upregulation of the mannose receptor CD206, which correlated positively with HbA1c levels, indicating a shift toward a permissive M2-like phenotype. Phagocytic uptake of Mtb was significantly impaired and inversely correlated with HbA1c. Antigen-presenting capacity was selectively compromised, with reduced CD80 and CD86 expression in DM and TB-DM groups, while HLA-DR remained unchanged. Intracellular Mtb killing was markedly diminished in diabetic macrophages. These findings demonstrate that chronic hyperglycaemia profoundly disrupts macrophage innate immunity, contributing to increased TB susceptibility and poor infection control in diabetic populations.

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HumansImmunity, InnateMacrophagesPhagocytosisMycobacterium tuberculosisFemaleMaleLectins, C-TypeMannose-Binding LectinsReceptors, Cell SurfaceMannose ReceptorTuberculosis, PulmonaryDiabetes Mellitus, Type 2Case-Control StudiesMiddle AgedBlood GlucoseAdultPhenotypeHost-Pathogen InteractionsGlycated HemoglobinCells, CulturedAntigen PresentationHyperglycemiaScavenger Receptors, Class AHyperglycaemiaTuberculosisJournal Article

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Alisha Arora, Sudhasini Panda, Kalpana Luthra, Anant Mohan, Yashdeep Gupta, Umesh Kumar, Archana Singh. 2026-08-04. Glycaemic burden disrupts innate immunity in TB by modulating CD206 expression and macrophage antimicrobial responses.. https://doi.org/10.1016/j.tube.2026.102799

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Journal Article resourceAdult subjectBlood Glucose subjectCase-Control Studies subjectCells, Cultured subjectDiabetes Mellitus, Type 2 subjectFemale subjectHumans subjectImmunity, Innate subjectJournal Article subjectMale subjectMiddle Aged subjectMycobacterium tuberculosis subjectPhenotype subject

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