title: Harnessing of TLR-mediated autophagy to combat mycobacteria in macrophages.
abstract: Autophagy, an evolutionary highly conserved process in virtually all eukaryotic cells, involves the sequestration of cytosol regions within double-membrane bound compartments and delivery of the contents to the lysosomes for degradation. Rapidly accumulating evidence has shown that autophagy is a component of innate immunity and is involved in host defense elimination of pathogens. Our previous studies show that Toll-like receptor 4 (TLR4) is a sensor for autophagy associated with innate immunity. We, now, further demonstrate that LPS or poly(I:C)-treatment significantly reduced mycobacterial viability in mouse macrophages. In addition, LPS reduction of mycobacterial viability was abrogated with the use of autophagy inhibitor 3-MA and in autophagy deficient macrophages. These findings demonstrate that TLR3 or TLR4 stimulation induces autophagy-mediated elimination of mycobacteria in macrophages. These results provide groundwork for therapeutic strategies directed at elimination of mycobacterial infections in macrophages.
authors.affiliation: Department of Medicine, Baylor College of Medicine, University of Houston Medical School, Houston, TX, USA.
authors.forename: Yi
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Department of Medicine, Baylor College of Medicine, University of Houston Medical School, Houston, TX, USA.
authors.forename: Elmoataz Abdel
authors.initials: EA
authors.lastname: Fattah
authors.affiliation: Department of Medicine, Baylor College of Medicine, University of Houston Medical School, Houston, TX, USA.
authors.forename: Xian-De
authors.initials: XD
authors.lastname: Liu
authors.affiliation: Pathology & Laboratory Medicine Department, University of Houston Medical School, Houston, TX, USA.
authors.forename: Chinnaswamy
authors.initials: C
authors.lastname: Jagannath
authors.affiliation: Department of Medicine, Baylor College of Medicine, University of Houston Medical School, Houston, TX, USA. Electronic address: teissa@bcm.edu.
authors.forename: N Tony
authors.initials: NT
authors.lastname: Eissa
mesh_terms: D000818:Animals; D001343:Autophagy / Q000276:immunology*; D007111:Immunity, Cellular; D007113:Immunity, Innate; D008264:Macrophages / Q000276:immunology* / Q000382:microbiology; D051379:Mice; D009164:Mycobacterium Infections / Q000276:immunology*; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D011956:Receptors, Cell Surface / Q000276:immunology; D015398:Signal Transduction; D051196:Toll-Like Receptor 3 / Q000276:immunology; D051197:Toll-Like Receptor 4 / Q000276:immunology
chemical_list: D011956:Receptors, Cell Surface; D051196:Toll-Like Receptor 3; D051197:Toll-Like Receptor 4
keywords: Autophagy; LPS; Mycobacteria tuberculosis; Toll-like Receptors