Abstract
Type 2 diabetes mellitus confers a threefold increased risk for tuberculosis, but the underlying immunological mechanisms are still largely unknown. Possible mediators of this increased susceptibility are short-chain fatty acids, levels of which have been shown to be altered in individuals with diabetes. We examined the influence of physiological concentrations of butyrate on cytokine responses to Mycobacterium tuberculosis (Mtb) in human peripheral blood mononuclear cells (PBMCs). Butyrate decreased Mtb-induced proinflammatory cytokine responses, while it increased production of IL-10. This anti-inflammatory effect was independent of butyrate's well-characterised inhibition of HDAC activity and was not accompanied by changes in Toll-like receptor signalling pathways, the eicosanoid pathway, or cellular metabolism. In contrast blocking IL-10 activity reversed the effects of butyrate on Mtb-induced inflammation. Alteration of the gut microbiota, thereby increasing butyrate concentrations, can reduce insulin resistance and obesity, but further studies are needed to determine how this affects susceptibility to tuberculosis.
Highlights
Tuberculosis (TB) is the second leading cause of death from an infectious disease worldwide [1]
In particular we investigated the effects of varying doses of acetate (C2), propionate (C3), and butyrate (C4) on H37Rv-induced cytokine responses, with RPMI as negative control and LPS as positive control (Figure 1)
We here show that SCFAs, especially C4, exhibit anti-inflammatory properties; low doses of C4 decreased Mycobacterium tuberculosis (Mtb)-induced proinflammatory cytokine responses on both the transcriptional level and the translational level, while production of IL-10 was increased
Summary
Tuberculosis (TB) is the second leading cause of death from an infectious disease worldwide [1]. Susceptibility to TB can be increased by several comorbidities, one of which is type 2 diabetes mellitus (DM) [2]. DM patients present with an overall threefold increased risk of developing active TB [3]. DM patients exhibit alterations in the immune response against Mycobacterium tuberculosis (Mtb), making them more susceptible to infection or progression towards active TB disease and less responsive to treatment [8,9,10,11]. DM patients have been associated with dysregulated cytokine responses to Mtb [14,15,16,17]. Whilst proinflammatory cytokines are necessary for protection against Mtb, anti-inflammatory cytokines may counteract these effects
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
