Macrophage Reprogramming by Mycolic Acid Promotes a Tolerogenic Response in Experimental Asthma

Abstract

These results document an innate-driven Mycobacterium tuberculosis MA-triggered immune regulatory mechanism in control of pulmonary allergic responses by converting macrophages into IFN-gamma-dependent tolerogenic antigen-presenting cells.

Towards understanding the functional diversity of cell wall mycolic acids of Mycobacterium tuberculosis

“…Free mycolic acids in these biofilms reportedly are derived from cell envelope glycosylated mycolates and are released by a trehalose dimycolate-specific serine esterase [122]. These new findings support the notion that free mycolic acids in tubercle granulomas may actively contribute to the delicate immune balance maintained in granuloma structures by exerting the divergent pro-and anti-inflammatory activities previously reported with isolated mycolic acids [108,116,117].…”

Liver X receptors contribute to the protective immune response against Mycobacterium tuberculosis in mice

“…In addition, M. tuberculosis contains an array of unique lipid components in its outer cell envelope that could act as potential LXR ligands. Mycolic acid, in particular, has been shown to trigger reprogramming of macrophage inflammatory functions along with a strong TLR-2-and TLR-4-independent interference with the lipid metabolism of the cells (16,51). Alternatively, oxysterols, as naturally occurring, host-derived ligands, may be responsible for LXR activation upon M. tuberculosis infection.…”

“…Hydroxymethylbilane synthase mRNA was used as reference housekeeping gene for normalization. The level of target mRNA, relative to the mean of the reference housekeeping gene, was calculated as previously described (51).…”

Tuberculosis: Pathophysiology, Clinical Features, and Diagnosis

“…9 Bacteria in droplets that bypass the mucociliary system and reach the alveoli are quickly surrounded and engulfed by alveolar macrophages, 7,8 the most abundant immune effector cells present in alveolar spaces. 10 These macrophages, the next line of host defense, are part of the innate immune system and provide an opportunity for the body to destroy the invading mycobacteria and prevent infection. 11 Macrophages are readily available phagocytic cells that combat many pathogens without requiring previous exposure to the pathogens.…”