Chronic hyperglycemia in response to Mycobacterium tuberculosis infection

An investigation explores the impact of chronic hyperglycemia on macrophage immune responses using a combination of cell culture and diabetic mouse models. The research specifically assesses how prolonged high glucose environments influence the innate defense capability of macrophages when challenged by Mycobacterium tuberculosis (Mtb) or inflammatory stimuli such as LPS.

Results reveal that although hyperglycemia alone increases baseline ROS production, it paradoxically dampens the macrophages' ability to elevate ROS levels in response to infection or inflammation. Moreover, the capacity to produce nitric oxide and other reactive nitrogen species is significantly reduced under hyperglycemic conditions. These findings suggest that chronic high glucose exposure may desensitize macrophages to vital immune triggers.

In addition to impaired oxidative responses, macrophages in a hyperglycemic state show a dysregulated cytokine profile. They produce lower levels of key pro-inflammatory cytokines like IL-1β and IL-6 and higher levels of the anti-inflammatory cytokine IL-10. This skewed cytokine response indicates a suppression of the classical inflammatory pathway, potentially facilitating immune evasion by pathogens.

Surface expression of important macrophage receptors such as TLR-4 and differentiation markers CD11b and CD11c is also significantly decreased, further limiting the immune competence of these cells. Together, these changes illustrate that chronic hyperglycemia undermines both the detection and destruction capacities of macrophages.

The study robustly concludes that sustained hyperglycemia alters the innate immune landscape by dampening macrophage responses to infection and inflammation. This may partly explain why individuals with poorly controlled diabetes are more susceptible to infections like tuberculosis.

References:

1. Chaubey, G.K., Modanwal, R., Dilawari, R., Talukdar, S., Dhiman, A., Chaudhary, S., Patidar, A., Raje, C.I. and Raje, M., 2024. Chronic hyperglycemia impairs anti-microbial function of macrophages in response to Mycobacterium tuberculosis infection. Immunologic Research, 72(4), pp.644-653.