Open AccessMycobacterium tuberculosis inhibition of phagolysosome biogenesis and autophagy as a host defence mechanism
Author(s) -
Deretic Vojo,
Singh Sudha,
Master Sharon,
Harris James,
Roberts Esteban,
Kyei George,
Davis Alex,
De Haro Sergio,
Naylor John,
Lee HuangHo,
Vergne Isabelle
Publication year - 2006
Publication title -
cellular microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.542
H-Index - 138
eISSN - 1462-5822
pISSN - 1462-5814
DOI - 10.1111/j.1462-5822.2006.00705.x
Subject(s) - phagosome , biology , phagolysosome , effector , autophagy , microbiology and biotechnology , rab , biogenesis , intracellular parasite , phosphatidylinositol , mycobacterium tuberculosis , acquired immune system , intracellular , gtpase , kinase , antigen , immunology , tuberculosis , biochemistry , gene , medicine , apoptosis , pathology
Summary A marquee feature of the powerful human pathogen Mycobacterium tuberculosis is its macrophage parasitism. The intracellular survival of this microorganism rests upon its ability to arrest phagolysosome biogenesis, avoid direct cidal mechanisms in macrophages, and block efficient antigen processing and presentation. Mycobacteria prevent Rab conversion on their phagosomes and elaborate glycolypid and protein trafficking toxins that interfere with Rab effectors and regulation of specific organellar biogenesis in mammalian cells. One of the major Rab effectors affected in this process is the type III phosphatidylinositol 3‐kinase hVPS34 and its enzymatic product phosphatidylinositol 3‐phosphate (PI3P), a regulatory lipid earmarking organellar membranes for specific trafficking events. PI3P is also critical for the process of autophagy, recently recognized as an effector of innate and adaptive immunity. Induction of autophagy by physiological, pharmacological or immunological signals, including the major antituberculosis Th1 cytokine IFN‐γ and its downstream effector p47 GTPase LRG‐47, can overcome mycobacterial phagosome maturation block and inhibit intracellular M. tuberculosis survival. This review summarizes the findings centred around the PI3P‐nexus where the mycobacterial phagosome maturation block and execution stages of autophagy intersect.