title: Autophagy protects against active tuberculosis by suppressing bacterial burden and inflammation.
abstract: Autophagy is a cell biological pathway affecting immune responses. In vitro, autophagy acts as a cell-autonomous defense against Mycobacterium tuberculosis, but its role in vivo is unknown. Here we show that autophagy plays a dual role against tuberculosis: antibacterial and anti-inflammatory. M. tuberculosis infection of Atg5(fl/fl) LysM-Cre(+) mice relative to autophagy-proficient littermates resulted in increased bacillary burden and excessive pulmonary inflammation characterized by neutrophil infiltration and IL-17 response with increased IL-1α levels. Macrophages from uninfected Atg5(fl/fl) LysM-Cre(+) mice displayed a cell-autonomous IL-1α hypersecretion phenotype, whereas T cells showed propensity toward IL-17 polarization during nonspecific activation or upon restimulation with mycobacterial antigens. Thus, autophagy acts in vivo by suppressing both M. tuberculosis growth and damaging inflammation.
authors.affiliation: Department of Molecular Genetics and Microbiology, University of New Mexico Health Sciences Center, Albuquerque, NM 87131, USA.
authors.forename: Eliseo F
authors.initials: EF
authors.lastname: Castillo
authors.forename: Alexander
authors.initials: A
authors.lastname: Dekonenko
authors.forename: John
authors.initials: J
authors.lastname: Arko-Mensah
authors.forename: Michael A
authors.initials: MA
authors.lastname: Mandell
authors.forename: Nicolas
authors.initials: N
authors.lastname: Dupont
authors.forename: Shanya
authors.initials: S
authors.lastname: Jiang
authors.forename: Monica
authors.initials: M
authors.lastname: Delgado-Vargas
authors.forename: Graham S
authors.initials: GS
authors.lastname: Timmins
authors.forename: Dhruva
authors.initials: D
authors.lastname: Bhattacharya
authors.forename: Hongliang
authors.initials: H
authors.lastname: Yang
authors.forename: Julie
authors.initials: J
authors.lastname: Hutt
authors.forename: C Rick
authors.initials: CR
authors.lastname: Lyons
authors.forename: Karen M
authors.initials: KM
authors.lastname: Dobos
authors.forename: Vojo
authors.initials: V
authors.lastname: Deretic
mesh_terms: D000818:Animals; D001343:Autophagy / Q000235:genetics / Q000276:immunology*; D000071187:Autophagy-Related Protein 5; D020381:Interleukin-17 / Q000276:immunology; D053582:Interleukin-1alpha / Q000235:genetics / Q000276:immunology; D008264:Macrophages / Q000276:immunology; D051379:Mice; D008822:Mice, Transgenic; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000276:immunology*; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D020556:Neutrophil Infiltration / Q000235:genetics / Q000276:immunology; D009504:Neutrophils / Q000276:immunology / Q000382:microbiology; D013601:T-Lymphocytes / Q000276:immunology / Q000382:microbiology; D014376:Tuberculosis / Q000235:genetics / Q000276:immunology* / Q000382:microbiology
chemical_list: C495773:Atg5 protein, mouse; D000071187:Autophagy-Related Protein 5; D020381:Interleukin-17; D053582:Interleukin-1alpha; D008869:Microtubule-Associated Proteins