Mycobacterium leprae efficiently deactivates a potent PAMP to evade host immune responses

Abstract

  Mycobacterium leprae, a causative pathogen of Hansen’s disease, is known to be less susceptible to host immune responses and capable of latent infection. However, the full mechanism underlying this phenomenon remains unclear. In this study, we identified PGL-III (phenolic glycolipid-III) as a potential PAMP (pathogen-associated molecular pattern) in M. leprae and demonstrated that it strongly activates macrophages via Mincle (macrophage-inducible C-type lectin receptor). Interestingly, within the M. leprae cell, PGL-III is converted to PGL-I through a single methylation event, completely losing its ligand activity for Mincle. Additionally, as PGL-III is present in only very small amounts in the bacterial cell compared to PGL-I, this metabolic conversion is presumed to occur rapidly. The rapid and efficient deactivation of immunostimulatory components can be interpreted as a host immune evasion mechanism of M. leprae. Further analysis of this pathway is expected to provide new therapeutic strategies for leprosy.