Follow-Up of Metabolic Markers During the Progression of Tuberculosis in BALB/c Mice

<jats:p>Background/Objectives: Mycobacterium tuberculosis is an intracellular bacterium that inhabits macrophage which displays diverse metabolic adaptations during the early pro-inflammatory stage (1-28 days) and a late anti-inflammatory stage (&amp;gt;28 to 120) of infection that favored the intracellular pathogen survival. During the early infection phase, macrophage are associated to pathogen eradication and a metabolic reprogramming characterized by enzymes that participate in glutamynolisis, like glutaminase (GLS) and glutamate dehydrogenase (GDH) that participate in glutamate oxidative deamination. However, to date, there is no evidence that non oxidative branch pentose phosphate, -which includes carbohydrate kinase-like protein (CARKL), transaldolase (TAL), transketolase (TKT), in addition the extracellular succinate sensor GPR91-, participates in the reconfiguration of the immune response in tuberculosis infection. To follow-up the aforementioned markers during the progression of tuberculosis in BALB/c mice. Methods: Male 8-week-old BALB/c mice were intratracheally infected with 2.5 × 10⁵ CFUs of M. tuberculosis H37Rv. Lung tissue samples (n=5/group) were collected over 60 days post-infection and analyzed by immunohistochemistry. Results: At previous post-infection days, expression of GDH, GPR91, CARKL and TAL reached a maximum on day 28, GLS on 60-day and no changes were seen in TKT. Conclusions: Changes in the expression of most markers on day 28 suggest that the pathogen is involved in the reprogramming of the Th2/M2 immune response in the early phase of tuberculosis infection. Findings provide additional insights about the follow-up during the early phase of infection based on the metabolic markers with potential implications in the mapping of macrophage targets for control of tuberculosis infection.</jats:p>