title: Aminopeptidase N facilitates entry and intracellular survival of Mycobacterium tuberculosis in monocytes.
abstract: OBJECTIVE
  Aminopeptidase N (CD13) is an ectoenzyme located in the outer membrane of a variety of cells. Proteomic profiling indicates an increased expression of CD13 in phagocytes during Mycobacterium tuberculosis infection. The purpose of this study was to investigate the role of CD13 on the internalization and intracellular survival of M. tuberculosis in monocytes.
  
  
  METHODS
  Magnetic nanoparticles and confocal microscopy were used to observe interactions between CD13 and M. tuberculosis. Mycobacterial entry and intracellular survival in monocytes were assessed with and without anti-CD13 antibody (WM15 and WM47) using flow cytometry and colony formation assay.
  
  
  RESULTS
  By using magnetic nanoparticles and confocal microscopy, M. tuberculosis was found to be capable of binding to either soluble CD13 or membranous CD13 on monocytes. Flow cytometry showed that pretreatment of monocytes with WM15 or WM47 reduced the number of intracellular M. tuberculosis. Collectively, the data suggest that CD13 is a binding and entry receptor for M. tuberculosis on monocytes. Treatment of infected monocytes showed a greater effect of WM47 than WM15 in reducing the intracellular colonization of M. tuberculosis, suggesting that specific epitopes of CD13 may play an important role modulating intracellular M. tuberculosis survival.
  
  
  CONCLUSIONS
  CD13 acts as a receptor for M. tuberculosis on human monocytes. The molecule facilitates internalization, and interaction of CD13 with an anti-CD13 antibody reduces intracellular M. tuberculosis survival.
authors.affiliation: Department of Laboratory Medicine, Mackay Memorial Hospital, Taipei, Taiwan; Department of Medicine, Mackay Medical College, New Taipei City, Taiwan.
authors.forename: Hsin-Tsung
authors.initials: HT
authors.lastname: Ho
authors.forename: I-Fang
authors.initials: IF
authors.lastname: Tsai
authors.forename: Chien-Liang
authors.initials: CL
authors.lastname: Wu
authors.forename: Yen-Ta
authors.initials: YT
authors.lastname: Lu
mesh_terms: D018826:CD13 Antigens / Q000378:metabolism*; D002478:Cells, Cultured / Q000382:microbiology; D005434:Flow Cytometry; D006801:Humans; D018613:Microscopy, Confocal; D009000:Monocytes / Q000201:enzymology*; D009169:Mycobacterium tuberculosis / Q000201:enzymology* / Q000302:isolation & purification; D040901:Proteomics / Q000379:methods; D014376:Tuberculosis / Q000201:enzymology / Q000382:microbiology* / Q000473:pathology
chemical_list: D018826:CD13 Antigens
keywords: CD13; Mycobacterium tuberculosis; aminopeptidase N; receptor; tuberculosis