Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
Critical Care
Published in: Critical Care 1/2019

Open Access 01-12-2019 | Nosocomial Pneumonia | Research

Alterations of the iNKT cell compartment in brain-injured patients

Authors: Allan Patinec, Jézabel Rocher, Mickael Vourc’h, Antoine Roquilly, Karim Asehnoune, Jacques Le Pendu

Published in: Critical Care | Issue 1/2019

Login to get access

Abstract

Background

Brain injury (BI) induces a state of immunodepression leading to pneumonia. We investigated the invariant natural killer T (iNKT) cell compartment.

Methods

This is an observational study in two surgical intensive care units (ICUs) of a single institution and a research laboratory. Clinical data and samples from a prospective cohort were extracted. Severe brain-injured patients (n = 33) and sex- and age-matched healthy donors (n = 40) were studied.

Results

We observed the presence of IL-10 in serum, a loss of IFN-γ and IL-13 production by peripheral blood mononuclear cells (PBMCs) following IL-2 stimulation, and downregulation of HLA-DR expression on both monocytes and B cells early after BI. Inversely, CD1d, the HLA class I-like molecule involved in antigen presentation to iNKT cells, was over-expressed on patients’ monocytes and B cells. The antigen-presenting activity to iNKT cells of PBMCs was increased in the patients who developed pneumonia, but not in those who remained free of infection. Frequencies of iNKT cells among PBMCs were dramatically decreased in patients regardless of their infection status. Following amplification, an increased frequency of CD4+ iNKT cells producing IL-4 was noticed in the group of patients free of infection compared with those who became infected and with healthy donors. Finally, serum from BI patients inhibited the iNKT cells’ specific response as well as the non-specific IL-2 stimulation of PBMCs, and the expression of the beta-2 adrenergic receptor was elevated at the surface of patients T lymphocytes.

Conclusions

We observed severe alterations of the iNKT cell compartment, including the presence of inhibitory serum factors. We demonstrate for the first time that the decreased capacity to present antigens is not a generalized phenomenon because whereas the expression of HLA-DR molecules is decreased, the capacity for presenting glycolipids through CD1d expression is higher in patients.
Appendix
Available only for authorised users
Literature
1.
Asehnoune K, Seguin P, Allary J, et al. Hydrocortisone and fludrocortisone for prevention of hospital-acquired pneumonia in patients with severe traumatic brain injury (Corti-TC): a double-blind, multicentre phase 3, randomised placebo-controlled trial. Lancet Respir Med. 2014;2:706–16.PubMedCrossRef
2.
Roquilly A, Mahe PJ, Seguin P, et al. Hydrocortisone therapy for patients with multiple trauma: the randomized controlled HYPOLYTE study. JAMA. 2011;305:1201–9.PubMedCrossRef
3.
Roquilly A, Feuillet F, Seguin P, et al. Empiric antimicrobial therapy for ventilator-associated pneumonia after brain injury. Eur Respir J. 2016;47:1219–28.PubMedCrossRef
4.
Bronchard R, Albaladejo P, Brezac G, et al. Early onset pneumonia: risk factors and consequences in head trauma patients. Anesthesiology. 2004;100:234–9.PubMedCrossRef
5.
Meisel C, Schwab JM, Prass K, et al. Central nervous system injury-induced immune deficiency syndrome. Nat Rev Neurosci. 2005;6:775–86.PubMedCrossRef
6.
Prass K, Meisel C, Höflich C, et al. Stroke-induced immunodeficiency promotes spontaneous bacterial infections and is mediated by sympathetic activation reversal by poststroke T helper cell type 1-like immunostimulation. J Exp Med. 2003;198:725–36.PubMedPubMedCentralCrossRef
7.
Deknuydt F, Roquilly A, Cinotti R, et al. An in vitro model of mycobacterial granuloma to investigate the immune response in brain-injured patients. Crit Care Med. 2013;41:245–54.PubMedCrossRef
8.
Hinson HE, Sheth KN. Manifestations of the hyperadrenergic state after acute brain injury. Curr Opin Crit Care. 2012;18:139–45.PubMedCrossRef
9.
Wong CHY, Jenne CN, Lee W-Y, et al. Functional innervation of hepatic iNKT cells is immunosuppressive following stroke. Science. 2011;334:101–5.PubMedCrossRef
10.
Porcelli S, Yockey C, Brenner M, et al. Analysis of T cell antigen receptor (TCR) expression by human peripheral blood CD4-8- alpha/beta T cells demonstrates preferential use of several V beta genes and an invariant TCR alpha chain. J Exp Med. 1993;178:1–16.PubMedCrossRef
11.
Bendelac A, Lantz O, Quimby M, et al. CD1 recognition by mouse NK1+ T lymphocytes. Science. 1995;268:863–5.PubMedCrossRef
12.
Montoya CJ, Pollard D, Martinson J, et al. Characterization of human invariant natural killer T subsets in health and disease using a novel invariant natural killer T cell-clonotypic monoclonal antibody, 6B11. Immunology. 2007;122:1–14.PubMedPubMedCentralCrossRef
13.
14.
Brennan PJ, Brigl M, Brenner MB. Invariant natural killer T cells: an innate activation scheme linked to diverse effector functions. Nat Rev Immunol. 2013;13:101–17.PubMedCrossRef
15.
American Thoracic Society. Infectious Diseases Society of America: guidelines for the management of adults with hospital-acquired, ventilator-associated, and healthcare-associated pneumonia. Am J Respir Crit Care Med. 2005;171:388–416.CrossRef
16.
Asehnoune K, Seguin P, Lasocki S, et al. Extubation success prediction in a multicentric cohort of patients with severe brain injury. Anesthesiology. 2017;127:338–46.PubMedCrossRef
17.
Connolly ES, Rabinstein AA, Carhuapoma JR, et al. Guidelines for the management of aneurysmal subarachnoid hemorrhage: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2012;43:1711–37.PubMedCrossRef
18.
Brain Trauma Foundation, American Association of Neurological Surgeons, Congress of Neurological Surgeons: guidelines for the management of severe traumatic brain injury. J Neurotrauma 2007; 24 Suppl 1:S1–106.
19.
Hunault J, Diswall M, J-CC F, et al. 3-fluoro- and 3,3-difluoro-3,4-dideoxy-KRN7000 analogues as new potent immunostimulator agents: total synthesis and biological evaluation in human invariant natural killer T cells and mice. J Med Chem. 2012;55:1227–41.PubMedCrossRef
20.
Roquilly A, David G, Cinotti R, et al. Role of IL-12 in overcoming the low responsiveness of NK cells to missing self after traumatic brain injury. Clin Immunol Orlando Fla. 2017;177:87–94.CrossRef
21.
Chenouard A, Chesneau M, Braza F, et al. Phenotype and functions of B cells in patients with acute brain injuries. Mol Immunol. 2015;68:350–6.PubMedCrossRef
22.
Gumperz JE, Miyake S, Yamamura T, et al. Functionally distinct subsets of CD1d-restricted natural killer T cells revealed by CD1d tetramer staining. J Exp Med. 2002;195:625–36.PubMedPubMedCentralCrossRef
23.
Lukaszewicz A-CC, Grienay M, Matthieu R-R, et al. Monocytic HLA-DR expression in intensive care patients: interest for prognosis and secondary infection prediction. Crit Care Med. 2009;37:2746–52.PubMed
24.
An B, Lim J-Y, Jeong S, et al. CD1d is a novel cell-surface marker for human monocytic myeloid-derived suppressor cells with T cell suppression activity in peripheral blood after allogeneic hematopoietic stem cell transplantation. Biochem Biophys Res Commun. 2018;495:519–25.PubMedCrossRef
25.
Oleinika K, Rosser EC, Matei DE, et al. CD1d-dependent immune suppression mediated by regulatory B cells through modulations of iNKT cells. Nat Commun. 2018;9:684.PubMedPubMedCentralCrossRef
26.
De Raedt S, De Vos A, Van Binst A-MM, et al. High natural killer cell number might identify stroke patients at risk of developing infections. Neurol Neuroimmunol Neuroinflamm. 2015;2(2):e71.PubMedPubMedCentralCrossRef
Metadata
Title
Alterations of the iNKT cell compartment in brain-injured patients
Authors
Allan Patinec
Jézabel Rocher
Mickael Vourc’h
Antoine Roquilly
Karim Asehnoune
Jacques Le Pendu
Publication date
01-12-2019
Publisher
BioMed Central
Published in
Critical Care / Issue 1/2019
Electronic ISSN: 1364-8535
DOI
https://doi.org/10.1186/s13054-019-2518-2

Other articles of this Issue 1/2019

Critical Care 1/2019 Go to the issue

Research

Microcirculatory perfusion disturbances following cardiac surgery with cardiopulmonary bypass are associated with in vitro endothelial hyperpermeability and increased angiopoietin-2 levels

Research

Dysbiosis of the intestinal microbiota in neurocritically ill patients and the risk for death

Letter

Passive leg cycling and electrical stimulation cannot preserve strength in sepsis

Research

The association between nutritional adequacy and 28-day mortality in the critically ill is not modified by their baseline nutritional status and disease severity

Letter

Does training level affect the accuracy of visual assessment of capillary refill time?

Letter

When circulatory death does not come in time in potential organ donors