Th1-Th2 polarisation and autophagy in the control of intracellular mycobacteria by macrophages.
Autophagy is a major intracellular pathway for the lysosomal degradation of long-lived cytoplasmic macromolecules and damaged or surplus organelles. More recently, autophagy has also been linked with innate and adaptive immune responses against intracellular pathogens, including Mycobacterium tuberculosis, which can survive within macrophages by blocking fusion of the phagosome with lysosomes. Induction of autophagy by the Th1 cytokine IFN-gamma enables infected macrophages to overcome this phagosome maturation block and inhibit the intracellular survival of mycobacteria. Conversely, the Th2 cytokines IL-4 and IL-13 inhibit autophagy in murine and human macrophages. We discuss how differential modulation of autophagy by Th1 and Th2 cytokines may represent an important feature of the host response to mycobacteria.
Harris
James
J
Institute of Molecular Medicine, Trinity College Dublin and St. James's Hospital, Dublin 8, Ireland. jaharris@tcd.ie
Master
Sharon S
SS
De Haro
Sergio A
SA
Delgado
Monica
M
Roberts
Esteban A
EA
Hope
Jayne C
JC
Keane
Joseph
J
Deretic
Vojo
V
D000818:Animals; D001343:Autophagy / Q000502:physiology*; D016207:Cytokines / Q000502:physiology*; D006801:Humans; D007113:Immunity, Innate; D007371:Interferon-gamma / Q000502:physiology; D018793:Interleukin-13 / Q000502:physiology; D015847:Interleukin-4 / Q000502:physiology; D008264:Macrophages / Q000382:microbiology* / Q000502:physiology*; D009169:Mycobacterium tuberculosis / Q000502:physiology*; D010588:Phagosomes; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology
D016207:Cytokines; D018793:Interleukin-13; D015847:Interleukin-4; D007371:Interferon-gamma