title: Impaired Recognition of Mycobacterium tuberculosis by Alveolar Macrophages From Diabetic Mice.
abstract: BACKGROUND
  Diabetes mellitus is associated with increased tuberculosis risk and severity. We previously reported that tuberculosis susceptibility in diabetic mice results from a delay in innate immune response to inhaled Mycobacterium tuberculosis, leading to delayed adaptive immune priming and, consequently, a higher plateau lung bacterial burden and greater immune pathology.
  
  
  METHODS
  We tested the capacity of alveolar macrophages from diabetic mice to phagocytose M. tuberculosis ex vivo and promote T-cell activation in vivo.
  
  
  RESULTS
  Alveolar macrophages from diabetic mice had reduced expression of CD14 and macrophage receptor with collagenous structure (MARCO), which recognize the bacterial cell wall component trehalose 6,6'-dimycolate (TDM). Diabetic alveolar macrophages exhibited reduced phagocytosis of M. tuberculosis or TDM-coated latex beads. This alveolar macrophage phenotype was absent in peritoneal and bone marrow-derived macrophages. Transfer of infected alveolar macrophages from diabetic mice into nondiabetic recipients confirmed an intrinsic alveolar macrophage defect that hindered T-cell priming. The diabetic alveolar macrophage phenotype depended in part on expression of the receptor for advanced glycation end products.
  
  
  CONCLUSIONS
  Reduced MARCO and CD14 expression contributes to defective sentinel function of alveolar macrophages, promoting tuberculosis susceptibility in diabetic hosts at a critical early step in the immune response to aerosol infection.
authors.affiliation: Department of Medicine, University of Massachusetts Medical School, Worcester.
authors.forename: Nuria
authors.initials: N
authors.lastname: Martinez
authors.affiliation: Australian Institute of Tropical Health and Medicine, James Cook University, Queensland, Australia.
authors.forename: Natkunam
authors.initials: N
authors.lastname: Ketheesan
authors.affiliation: Department of Medicine, University of Massachusetts Medical School, Worcester.
authors.forename: Kim
authors.initials: K
authors.lastname: West
authors.affiliation: Department of Medicine, University of Massachusetts Medical School, Worcester.
authors.forename: Therese
authors.initials: T
authors.lastname: Vallerskog
authors.affiliation: Department of Medicine, University of Massachusetts Medical School, Worcester.
authors.forename: Hardy
authors.initials: H
authors.lastname: Kornfeld
mesh_terms: D000818:Animals; D003920:Diabetes Mellitus / Q000276:immunology*; D004198:Disease Susceptibility; D015870:Gene Expression; D018950:Lipopolysaccharide Receptors / Q000032:analysis; D008213:Lymphocyte Activation; D016676:Macrophages, Alveolar / Q000737:chemistry / Q000276:immunology* / Q000382:microbiology*; D008297:Male; D008810:Mice, Inbred C57BL; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D010587:Phagocytosis; D011971:Receptors, Immunologic / Q000032:analysis
chemical_list: D018950:Lipopolysaccharide Receptors; C092228:Marco protein, mouse; D011971:Receptors, Immunologic
keywords: CD14; MARCO; Mycobacterium tuberculosis; alveolar macrophages; diabetes; phagocytosis