Role of IL-12 in overcoming the low responsiveness of NK cells to missing self after traumatic brain injury

International audienceBlood samples from 32 patients with severe Traumatic brain injury (TBI) were studied and compared with 11 cardiac surgery patients, and 29 healthy controls. A dramatic decreased expression of HLA class I molecules on monocytes was associated with increased KIR+ NK cell frequency in TBI patients. Overall, the phenotype of TBI NK cells marked by KIR and CD57 expression and lower level of NKp46 and DNAM-1 reflected a differentiated state. The NK-cell response to missing self was marked by lower degranulation and lower IFN-γ production after stimulation with HLA class I deficient cell line. In contrast, the NK-cell ADCC was not altered. IL-12 was able to restore both IFN-γ production and the cytotoxicity capacities of NK cells. This study provides the first extensive description of the phenotype and functions of NK cells in TBI patients. Further evaluation of IL-12 treatment to overcome immunosuppression-induced nosocomial infections is warranted

Phenotype and functions of B cells in patients with acute brain injuries

International audienceBackground: Brain injuries (BI) induce a state of systemic immunosuppression, leading to a high risk of pneumonia. In this pilot study, we investigated the status of B cell compartment in BI patients.Methods: A prospective observational study was performed in 2 intensive care units in a university hospital. Blood samples were collected in 14 patients at day 1 and day 7 after acute BI. The phenotype and the ability of B cells to secrete IL-10 were compared to 11 healthy volunteers (HV).Results: Among the circulating lymphocytes, the frequency of B cells was significantly higher in BI patients compared to HV (p < 0.001). B cells from BI patients displayed an activated profil on day 7 after BI, reflected by a significantly higher proportion of CD27 + memory (p = 0.01) and CD27 + IgD − switched memory B cells (p = 0.02), as well as a significantly higher blood level of IgA (p = 0.001) and IgM (p < 0.001) as compared to day 1. The frequency of IL-10 secreting B cells (IL-10 + B cells) on day 1 and day 7 was significantly lower in BI patients compared to HV (p < 0.05). Interestingly, we observed that all BI patients with high frequency of IL-10 + B cells on day 1 displayed an episode of pneumonia, and had a longer duration of mechanical ventilation and ICU stay compared to BI patients with low proportion of IL-10 + B cells.Conclusion: This study provides an extensive description of the phenotype and function of B cells in BI patients. Our results suggest that IL-10 + B cells could play a major role in immunosuppression after BI

Data_Sheet_2_A network meta-analysis of therapeutic and prophylactic management of vasospasm on aneurysmal subarachnoid hemorrhage outcomes.docx

BackgroundVasospasm and cerebral ischemia after aneurysmal subarachnoid hemorrhage are associated with mortality and poor neurological outcomes. We studied the efficacy of all available strategies targeting vasospasm and cerebral ischemia on outcomes in a network meta-analysis.MethodsWe searched EMBASE and MEDLINE databases from 1 January 1990 and 28 November 2021 according to PRISMA guidelines. Randomized controlled trials and longitudinal studies were included. All curative or preventive strategies targeting vasospasm and/or cerebral ischemia were eligible. A network meta-analysis was performed to compare all interventions with one another in a primary (randomized controlled trials only) and a secondary analysis (both trials and longitudinal studies). Mortality by 3 months was the primary outcome. Secondary outcomes were vasospasm, neurological outcome by 3 months, and dichotomized as “good” or “poor” recovery according to each study definition.ResultsA total of 2,382 studies were screened which resulted in the selection of 192 clinical trials (92 (47.9%) and 100 cohorts (52.1%) and the inclusion of 41,299 patients. In randomized controlled studies, no strategy decreased mortality by 3 months. Statins (0.79 [0.62–1]), tirilazad (0.82 [0.69–0.97]), CSF drainage (0.47 [0.29–0.77]), and clazosentan (0.51 [0.36–0.71]) significantly decreased the incidence of vasospasm. Cilostazol was the only treatment associated with improved neurological outcomes by 3 months in the primary (OR 1.16, 95% CI [1.05–1.28]) and secondary analyses (OR 2.97, 95% CI [1.39–6.32]).DiscussionIn the modern era of subarachnoid hemorrhage, all strategies targeting vasospasm failed to decrease mortality. Cilostazol should be confirmed as a treatment to improve neurological outcomes. The link between vasospasm and neurological outcome appears questionable.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=116073, identifier: PROSPERO CRD42018116073.</p

Gating strategy used to identify blood DC subsets and intracellular cytokines production in DCs in whole blood stimulated with TLR ligands.

<p>Whole blood samples were incubated with TLR3, 4, 7/8 or 9 ligands for 3.5-hour and then stained for identification of myeloid DC (HLA-DR+, Lin-, CD11c+, CD123-) and plasmacytoid DC (HLA-DR+, lin−, CD11c−, CD123+) together with intracellular cytokine production (TNFα, IL-12, IFNα).</p

Time course of TLR-induced production of TNF-α and IL-12 in circulating mDCs from patients with aneurysmal subarachnoid hemorrhage.

<p>Intracellular cytokine measurement was performed in circulating mDCs from SAH patients (N = 21) on days 2, 5 and 10 and from HC (N = 11). The percentages of mDCs expressing TNF-α or IL-12 were assessed after a 3.5-hour <i>ex vivo</i> stimulation with (<b>A</b>) polyIC (TLR-3 agonist), (<b>B</b>) lipopolysaccharide (TLR-4 agonist) or (<b>C</b>) CL097 (TLR-7/8 agonist). The percentage of positive DCs without TLR-stimulation was below 1% (data not shown). The results are presented as percentages of mDCs expressing TNF-α (%TNF-α⁺) or IL-12 (% IL-12⁺). Plots represent median (Interquartile ranges). HC: healthy controls. mDCs: myeloid dendritic cells. SAH: aneurysmal subarachnoid hemorrhage. TNF-α: tumour necrosis factor -α. IL-12: intreleukin-12. * <i>P</i><0.05.</p