The role of autophagy in host defence against Mycobacterium tuberculosis infection.
Autophagy is a vital homeostatic process triggered by starvation and other cellular stresses, in which cytoplasmatic cargo is targeted for degradation in specialized structures termed autophagosomes. Autophagy is involved in nutrient regeneration, protein and organelle degradation, but also in clearance of intracellular pathogens such as Mycobacterium tuberculosis, the causative agent of tuberculosis. Recent studies suggest that induction of autophagy in macrophages is an effective mechanism to enhance intracellular killing of M. tuberculosis, and that the ability of the pathogen to inhibit this process is of paramount importance for its survival. Patient studies have shown genetic associations between tuberculosis and the autophagy gene IRGM, as well as with several genes indirectly involved in autophagy. In this review we will discuss the complex interplay between M. tuberculosis and autophagy, as well as the effect of polymorphisms in autophagy-related genes on susceptibility to tuberculosis.
Department of Internal Medicine, Radboud University Nijmegen Medical Centre, and Nijmegen Institute for Infection, Inflammation and Immunity (N4i), Geert Grooteplein Zuid 8, 6525 GA Nijmegen, The Netherlands.
Mário
M
Songane
Johanneke
J
Kleinnijenhuis
Mihai G
MG
Netea
Reinout
R
van Crevel
D001343:Autophagy / Q000235:genetics*; D016022:Case-Control Studies; D002762:Cholecalciferol / Q000235:genetics; D016207:Cytokines / Q000235:genetics; D019204:GTP-Binding Proteins / Q000235:genetics*; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D054884:Host-Pathogen Interactions; D006801:Humans; D009169:Mycobacterium tuberculosis / Q000235:genetics* / Q000472:pathogenicity; D014376:Tuberculosis / Q000235:genetics / Q000473:pathology / Q000503:physiopathology*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
D016207:Cytokines; D014409:Tumor Necrosis Factor-alpha; D002762:Cholecalciferol; D019204:GTP-Binding Proteins; C513539:IRGM protein, human