title: An in vitro model of mycobacterial granuloma to investigate the immune response in brain-injured patients.
abstract: OBJECTIVE
  We investigated the overall immune response to pathogens in brain-injured patients, and assessed its relationship to nosocomial pneumonia.
  
  
  METHODS
  Observational study.
  
  
  METHODS
  Two surgical ICUs of a single institution.
  
  
  METHODS
  Severe brain-injured patients (n = 32) requiring mechanical ventilation and sex- and age-matched healthy donors (n = 25).
  
  
  METHODS
  None.
  
  
  RESULTS
  We evaluated, ex vivo, the ability of peripheral blood mononuclear cells from brain injury patients to develop an effective granulomatous response to mycobacteria. Thirty-two consecutive patients (25 traumatic brain injured and seven subarachnoid hemorrhage) were included. Median Glasgow Coma Scale was 7 (5-8). Thirteen (41%) patients developed nosocomial pneumonia. Peripheral blood mononuclear cells from brain-injured patients with nosocomial pneumonia generated significantly fewer mature granulomas compared with brain-injured patients without nosocomial pneumonia and with healthy donors. The percentage of multinucleated giant cells was lower in brain-injured patients without nosocomial pneumonia (1% [range: 0%-7%]) and in brain-injured patients with nosocomial pneumonia (4% [range: 2%-5%]) compared with healthy donors (20% [range: 15%-28%]). The blood levels of γδ T cells were significantly increased in brain-injured patients without nosocomial pneumonia (66% [range: 34%-69%]) compared with healthy donors (23% [range: 8%-61%]) and was not altered in brain-injured patients with nosocomial pneumonia (31% [range: 12%-44%]). The percentage of γδ T cells in granulomas was significantly decreased in brain injury patients with nosocomial pneumonia (5% [range: 4%-43%]) compared with healthy donors (43% [range: 19%-54%]) and was not significantly altered in brain-injured patients without nosocomial pneumonia (26% [range: 10%-41%]). The blood levels of natural killer cells were not altered in brain-injured patients. The percentage of natural killer cells in granulomas was significantly decreased in brain-injured patients with nosocomial pneumonia (3% [range: 1%-9%]) compared with brain-injured patients without nosocomial pneumonia (16% [range: 6%-29%]) and with healthy donors (17% [range: 10%-29%]).
  
  
  CONCLUSIONS
  Brain-injured patients experienced a maturation defect of the ex vivo granulomatous response involving monocytes as well as natural killer cells and γδ T cells.
authors.affiliation: INSERM, Unité 892, Institut de Recherche Thérapeutique, Université de Nantes, Nantes, France.
authors.forename: Florence
authors.initials: F
authors.lastname: Deknuydt
authors.forename: Antoine
authors.initials: A
authors.lastname: Roquilly
authors.forename: Raphaël
authors.initials: R
authors.lastname: Cinotti
authors.forename: Frédéric
authors.initials: F
authors.lastname: Altare
authors.forename: Karim
authors.initials: K
authors.lastname: Asehnoune
mesh_terms: D056704:Adaptive Immunity; D000328:Adult; D001930:Brain Injuries / Q000276:immunology*; D016022:Case-Control Studies; D002478:Cells, Cultured; D005260:Female; D005602:France / Q000453:epidemiology; D015726:Giant Cells / Q000378:metabolism; D006099:Granuloma / Q000276:immunology*; D006801:Humans; D007113:Immunity, Innate; D016867:Immunocompromised Host / Q000276:immunology*; D066298:In Vitro Techniques; D007362:Intensive Care Units; D007694:Killer Cells, Natural / Q000378:metabolism; D008297:Male; D016555:Matched-Pair Analysis; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism; D009163:Mycobacterium bovis / Q000276:immunology*; D053717:Pneumonia, Ventilator-Associated / Q000453:epidemiology / Q000276:immunology*; D013345:Subarachnoid Hemorrhage / Q000276:immunology*; D013601:T-Lymphocytes / Q000378:metabolism