An in vitro model of mycobacterial granuloma to investigate the immune response in brain-injured patients

Crit Care Med. 2013 Jan;41(1):245-54. doi: 10.1097/CCM.0b013e3182676052.

Abstract

Objective: We investigated the overall immune response to pathogens in brain-injured patients, and assessed its relationship to nosocomial pneumonia.

Design: Observational study.

Setting: Two surgical ICUs of a single institution.

Patients: Severe brain-injured patients (n = 32) requiring mechanical ventilation and sex- and age-matched healthy donors (n = 25).

Interventions: None.

Measurements and main 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptive Immunity
  • Adult
  • Brain Injuries / immunology*
  • Case-Control Studies
  • Cells, Cultured
  • Female
  • France / epidemiology
  • Giant Cells / metabolism
  • Granuloma / immunology*
  • Humans
  • Immunity, Innate
  • Immunocompromised Host / immunology*
  • In Vitro Techniques
  • Intensive Care Units
  • Killer Cells, Natural / metabolism
  • Male
  • Matched-Pair Analysis
  • Middle Aged
  • Monocytes / metabolism
  • Mycobacterium bovis / immunology*
  • Pneumonia, Ventilator-Associated / epidemiology
  • Pneumonia, Ventilator-Associated / immunology*
  • Subarachnoid Hemorrhage / immunology*
  • T-Lymphocytes / metabolism