title: IL-6 inhibits IFN-γ induced autophagy in Mycobacterium tuberculosis H37Rv infected macrophages.
abstract: The significance of IL-6 production in tuberculosis is yet to be fully elucidated, although it is known for quite some time that IL-6 interferes with IFN-γ induced signal. In order to know which cellular process induced by IFN-γ is actually counteracted by IL-6, we studied the role of IL-6 on IFN-γ induced autophagy formation in virulent Mycobacterium tuberculosis infection in THP-1 cells, since it is well characterized that induction of autophagy by IFN-γ eliminates intracellular mycobacterium by overcoming the phagosome maturation block imposed by bacilli. We report here that IL-6 inhibits both IFN-γ and starvation induced autophagy in M. tuberculosis H37Rv infected cells. M. tuberculosis H37Rv infection results in time dependent production of IL-6 in THP-1 cells and neutralization of this endogenous IL-6 by anti-IL-6 antibody significantly enhances the IFN-γ mediated killing of the intracellular bacteria. IL-6 time dependently lowers Atg12-Atg5 complex and therefore inhibits autophagosome biogenesis rather than autophagolysosome formation. IL-6 also affects IFN-γ mediated stimulation of mTOR, p-38 and JNK pathways. These results clearly indicate that virulent mycobacteria strategically upregulate IL-6 production to combat innate immunity.
authors.affiliation: Division of Cell Biology and Immunology, Institute of Microbial Technology (CSIR), Chandigarh 160036, India.
authors.forename: Rajesh Kumar
authors.initials: RK
authors.lastname: Dutta
authors.forename: Mahesh
authors.initials: M
authors.lastname: Kathania
authors.forename: Manoj
authors.initials: M
authors.lastname: Raje
authors.forename: Sekhar
authors.initials: S
authors.lastname: Majumdar
mesh_terms: D001343:Autophagy / Q000502:physiology*; D002460:Cell Line; D004797:Enzyme-Linked Immunosorbent Assay; D005455:Fluorescent Antibody Technique; D006801:Humans; D007371:Interferon-gamma / Q000502:physiology*; D015850:Interleukin-6 / Q000502:physiology*; D008264:Macrophages / Q000382:microbiology*; D018613:Microscopy, Confocal; D009169:Mycobacterium tuberculosis / Q000302:isolation & purification* / Q000472:pathogenicity
chemical_list: D015850:Interleukin-6; D007371:Interferon-gamma