Metabolic and Innate Immune Cues Merge into a Specific Inflammatory Response via the UPR

Erratum in : Metabolic and Innate Immune Cues Merge into a Specific Inflammatory Response via the UPR. [Cell. 2019]International audienceInnate immune responses are intricately linked with intracellular metabolism of myeloid cells. Toll-likereceptor (TLR) stimulation shifts intracellular metabolism toward glycolysis, while anti-inflammatorysignals depend on enhanced mitochondrial respiration. How exogenous metabolic signals affect theimmune response is unknown. We demonstrate that TLR-dependent responses of dendritic cells (DC)are exacerbated by a high fatty acid (FA) metabolic environment. FA suppress the TLR-inducedhexokinase activity and perturb tricarboxylic acid cycle metabolism. These metabolic changesenhance mitochondrial reactive oxygen species (mtROS) production and, in turn, the unfolded proteinresponse (UPR) leading to a distinct transcriptomic signature, with IL-23 as hallmark. Interestingly,chemical or genetic suppression of glycolysis was sufficient to induce this specific immune response.Conversely, reducing mtROS production or DC-specific deficiency in XBP1 attenuated IL-23expression and skin inflammation in an IL-23-dependent model of psoriasis. Thus, fine-tuning of innateimmunity depends on optimization of metabolic demands and minimization of mtROS-induced UPR

Fibroblastome à cellules géantes de présentation atypique

International audienceBACKGROUND: Giant cell fibroblastoma is a specific entity that belongs to the dermatofibrosarcoma protuberans spectrum. We report an original case with an atypical clinical presentation. CASE REPORT: A four-year-old male child presented with a perineoscrotal mass, present since the age of one year. This lesion was initially a bluish perineal macule that grew rapidly after a traumatic injury. Physical examination showed a large flaccid bi-lobed tumour originating from the posterior border of the left of the scrotum to the anal margin. A haemolymphangioma was clinically suspected and the results of ultrasound and MRI were consistent with this diagnosis. Because of the discomfort and the atypical clinical presentation, local surgical resection was performed. Histological examination did not confirm the clinical assumption but revealed a giant cell fibroblastoma. Because of the location of this tumour, a secondary surgical procedure was carried out using the "Slow-Mohs" technique. DISCUSSION: This case is particularly interesting because of the clinical pseudo-angiomatous presentation of this tumour. Use of the "Slow-Mohs" technique allowed sparing of tissue. No recurrence was noted after 3 years of follow-up

Effectiveness and safety of dupilumab for the treatment of prurigo nodularis in a French multicenter adult cohort of 16 patients.

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Plasma fractalkine is a sustained marker of disease severity and outcome in sepsis patients

INTRODUCTION: Fractalkine is a chemokine implicated as a mediator in a variety of inflammatory conditions. Knowledge of fractalkine release in patients presenting with infection to the Intensive Care Unit (ICU) is highly limited. The primary objective of this study was to establish whether plasma fractalkine levels are elevated in sepsis and associate with outcome. The secondary objective was to determine whether fractalkine can assist in the diagnosis of infection upon ICU admission. METHODS: Fractalkine was measured in 1103 consecutive sepsis patients (including 271 patients with community-acquired pneumonia (CAP)) upon ICU admission and at days 2 and 4 thereafter; in 73 ICU patients treated for suspected CAP in whom this diagnosis was refuted in retrospect; and in 5 healthy humans intravenously injected with endotoxin. RESULTS: Compared to healthy volunteers, sepsis patients had strongly elevated fractalkine levels. Fractalkine levels increased with the number of organs failing, were higher in patients presenting with shock, but did not vary by site of infection. Non-survivors had sustained elevated fractalkine levels when compared to survivors. Fractalkine was equally elevated in CAP patients and patients treated for CAP but in whom the diagnosis was retrospectively refuted. Fractalkine release induced by intravenous endotoxin followed highly similar kinetics as the endothelial cell marker E-selectin. CONCLUSIONS: Plasma fractalkine is an endothelial cell derived biomarker that, while not specific for infection, correlates with disease severity in sepsis patients admitted to the ICU