An In Vitro Model of Mycobacterial Granuloma to Investigate the Immune Response in Brain-Injured Patients

作者：Deknuydt Florence^*; Roquilly Antoine; Cinotti Raphael; Altare Frederic; Asehnoune Karim

来源：Critical Care Medicine, 2013, 41(1): 245-254.

DOI：10.1097/CCM.0b013e3182676052

• brain injury
• cellular immunity
• granulomas
• immunosuppression
• natural killer cells
• nosocomial pneumonia
• gamma delta t cells

Objective: We investigated the overall immune response to pathogens in brain-injured patients, and assessed its relationship to nosocomial pneumonia. %26lt;br%26gt;Design: Observational study. %26lt;br%26gt;Setting: Two surgical ICUs of a single institution. %26lt;br%26gt;Patients: Severe brain-injured patients (n = 32) requiring mechanical ventilation and sex- and age-matched healthy donors (n = 25). %26lt;br%26gt;Interventions: None. %26lt;br%26gt;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 gamma delta 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 gamma delta 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%]). %26lt;br%26gt;Conclusions: Brain-injured patients experienced a maturation defect of the ex vivo granulomatous response involving monocytes as well as natural killer cells and gamma delta T cells. (Crit Care Med 2013; 41:245-254)

• 出版日期2013-1