title: The Defect in Autophagy Induction by Clinical Isolates of Mycobacterium Tuberculosis Is Correlated with Poor Tuberculosis Outcomes.
abstract: BACKGROUND
  Tuberculosis (TB) represents a major global health problem. The prognosis of clinically active tuberculosis depends on the complex interactions between Mycobacterium tuberculosis (Mtb) and its host. In recent years, autophagy receives particular attention for its role in host defense against intracellular pathogens, including Mtb. In present study, we aim to investigate the relationship of autophagy induction by clinical isolates of Mtb with the clinical outcomes in patients with TB.
  
  
  RESULTS
  We collected 185 clinical isolates of Mtb, and determined the effect of these Mtb isolates on autophagy induction in macrophages. It was found that most of clinical isolates of Mtb were able to induce autophagosome formation in macrophages, however, the autophagy-inducing ability varied significantly among different isolates. Of importance, our results revealed that patients infected by Mtb with poor autophagy-inducing ability displayed more severe radiographic extent of disease (p<0.001), and were more likely to have unfavorable treatment outcomes (p<0.001). No significant association was observed between the extent of Mtb-induced autophagy with some socio-demographic characteristics (such as gender, age and tobacco consumption), and some laboratory tests (such as hemoglobin, leukocyte count and erythrocyte sedimentation rate). Furthermore, results from logistic regression analysis demonstrated that the defect in autophagy induction by clinical isolates of Mtb was an independent risk factor for far-advanced radiographic disease (aOR 4.710 [1.93-11.50]) and unfavorable treatment outcomes (aOR 8.309 [2.22-28.97]) in TB.
  
  
  CONCLUSIONS
  These data indicated that the defect in autophagy induction by Mtb isolates increased the risk of poor clinical outcomes in TB patients, and detection of clinical isolates-induced autophagosome formation might help evaluate the TB outcomes.
authors.affiliation: Institute for Immunobiology, Department of Immunology, Shanghai Medical College of Fudan University, Shanghai 200032, P.R. China.
authors.forename: Furong
authors.initials: F
authors.lastname: Li
authors.affiliation: Institute for Immunobiology, Department of Immunology, Shanghai Medical College of Fudan University, Shanghai 200032, P.R. China.
authors.forename: Bo
authors.initials: B
authors.lastname: Gao
authors.affiliation: Jiangsu Key Laboratory of Infection and Immunity, Institutes of Biology and Medical Sciences, Soochow University, Suzhou 215006, P.R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Xu
authors.affiliation: Department of Respiratory Medicine, Affiliated Hospital of Zunyi Medical College, Zunyi 563000, P.R. China.
authors.forename: Ling
authors.initials: L
authors.lastname: Chen
authors.affiliation: Institute for Immunobiology, Department of Immunology, Shanghai Medical College of Fudan University, Shanghai 200032, P.R. China.|Jiangsu Key Laboratory of Infection and Immunity, Institutes of Biology and Medical Sciences, Soochow University, Suzhou 215006, P.R. China.
authors.forename: Sidong
authors.initials: S
authors.lastname: Xiong
mesh_terms: D000328:Adult; D000818:Animals; D000995:Antitubercular Agents; D001343:Autophagy; D002460:Cell Line; D005260:Female; D054884:Host-Pathogen Interactions; D006801:Humans; D008264:Macrophages / Q000382:microbiology* / Q000473:pathology; D008297:Male; D051379:Mice; D008875:Middle Aged; D009169:Mycobacterium tuberculosis / Q000302:isolation & purification* / Q000502:physiology*; D011379:Prognosis; D016896:Treatment Outcome; D014376:Tuberculosis / Q000175:diagnosis* / Q000453:epidemiology / Q000503:physiopathology* / Q000628:therapy
chemical_list: D000995:Antitubercular Agents
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