Our results indicate that MtbDNA induced phenotypical changes, the significant production of TNF-α, and autophagy confirmed by the augmented expression of immunity related GTPase M (IRGM) and autophagy related ATG16L1 genes in M1 macrophages, whereas M2 macrophages exhibited limited responses.
The analysis showed that IRGMrs10065172 and rs4859846 were significantly associated with tuberculosis risk in all genetic models whereas the latent tuberculosis infection group in 1 study was excluded.
Thus, IRGM polymorphism differences between latent and active TB suggests that genetic differences in autophagy might partly affect host TB infection status.
Human immunity-related GTPase M (IRGM) is found to play an important role in defense against intracellular pathogen Mycobacterium tuberculosis (M. tuberculosis) in vitro by regulating autophagy.
Patient studies have shown genetic associations between tuberculosis and the autophagy gene IRGM, as well as with several genes indirectly involved in autophagy.
Recent data suggest that autophagy is important for intracellular killing of Mycobacterium tuberculosis, and polymorphisms in the autophagy gene IRGM have been linked with susceptibility to tuberculosis (TB) among African-Americans, and with TB caused by particular M. tuberculosis genotypes in Ghana.
IRGC is not involved in immunity, but the human IRGM gene plays a role in autophagy-targeted destruction of Mycobacterium tuberculosis (BCG) and Salmonella typhimurium.
Our results, including those of luciferase reporter gene assays with the IRGM variants -261C and -261T, suggest a role for IRGM and autophagy in protection of humans against natural infection with M. tuberculosis EUAM clades.
Three of these IFN-gamma-dependent mechanisms have been implicated in defense against M. tuberculosis: inducible nitric oxide synthase (iNOS), phagosome oxidase (phox), and the phagosome-associated GTPase LRG-47.