Fishing for Answers in Human Mycobacterial Infections

Abstract

Two recent studies (Cambier et al., 2017; Madigan et al., 2017) reveal in vivo functions for specific phenolic glycolipids (PGLs) in the mycobacteria that cause tuberculosis or leprosy. M. tuberculosis (and M. marinum) PGL promotes bacterial spread to growth-permissive macrophages, while M. leprae PGL-1 induces macrophages to cause nerve demyelination characteristic of human leprosy.

Figure 1.. In Vivo Functions for Species-Specific Phenolic Glycolipids in Mycobacteria

Mycobacterial phenolic glycolipids (PGLs) have a common core structure, but differ in their species-specific glycosylation and carbohydrate modifications. M. marinum infection in the zebrafish hindbrain ventricle leads to recruitment of brain-resident macrophages (ResM) and phagocytosis of the mycobacteria. M. marinum-specific PGL depends on STING cytosolic signaling (directly or indirectly) to induce chemokine CCL2 expression in ResM. CCR2-expressing circulating monocytes are subsequently attracted and M. marinum escape into those more growth-permissive cells. M. leprae PGL-1 in infected monocytes induces nitric oxide synthase and pathologic amounts of nitric oxide, which leads to nerve damage caused by mitochondrial damage and demyelination in areas of intimate contact of the infected macrophage with axons.