Chronic hyperglycemia drives alterations in macrophage effector function in pulmonary tuberculosis

Panda, S.; Seelan, D. M.; Faisal, S.; Luthra, K.; Palanichamy, J. K.; Mohan, A.; Vikram, N. K.; Gupta, N. K.; Ramakrishnan, L.; Singh, A.

doi:10.1101/2022.01.18.476721

bioRxiv · 10.1101/2022.01.18.476721

Chronic hyperglycemia drives alterations in macrophage effector function in pulmonary tuberculosis

Panda, S.·Seelan, D. M.·Faisal, S.·Luthra, K.·Palanichamy, J. K.·Mohan, A.·Vikram, N. K.·Gupta, N. K.·Ramakrishnan, L.·Singh, A.

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Abstract

BackgroundThe rising prevalence of Diabetes mellitus (DM) in high TB endemic countries has the potential to adversely affect sustainability of TB control since DM can lead to alterations in both innate and adaptive immune response constituting as a risk factor for development of active tuberculosis (TB). The impact of hyperglycemia on TB specific innate immune response in terms of macrophage functions remains poorly addressed. Material and methodsMacrophage effector functions in diabetic and non-diabetic individuals with and without PTB infection as well as non-diabetic-uninfected controls (fifty individuals in each group) were assessed. Phagocytic capacity against BCG and surface expression of PRRs (CD11b, CD14, CD206, MARCO and TLR2) were measured via flow cytometry. Effector molecules (ROS and NO) were assessed via DCFDA and Griess reaction respectively. ResultsA systematic dysregulation in phagocytic capacity with concurrent alterations in expression pattern of key PRRs (CD11b, MARCO and CD206) and effector molecules (ROS and NO) was observed in diabetic individuals with PTB. These altered macrophage functions were positively correlated with increase in disease severity in diabetic individuals. ConclusionOur results highlight several key patterns of immune dysregulation against M.Tb under hyperglycemic conditions. A significant reduction in macrophage effector functions in infected diabetic individuals which further correlated with increase in disease severity reveals a negative impact of hyperglycemia with aetiology and pathological progression of TB.

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Panda, S., Seelan, D. M., Faisal, S., Luthra, K., Palanichamy, J. K., Mohan, A., Vikram, N. K., Gupta, N. K., Ramakrishnan, L., Singh, A.. 2022-01-18. Chronic hyperglycemia drives alterations in macrophage effector function in pulmonary tuberculosis. https://doi.org/10.1101/2022.01.18.476721

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