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Microperforated plates (MPP) are traditionally used to advantageously absorb acoustic waves in sound control technologies. However, less is known concerning the additional structural damping they can induce. The latter is activated through exchanges in the viscous and thermal boundary layers near the fluid-structure interface of the microperforations. MPPs therefore offer an alternative to, or can be used together with, viscoelastic materials, commonly implemented to damp vibrations at medium and high frequencies. In this work, the structural damping capabilities of MPP are investigated. To this end, the damping performance of a finite size MPP is explored analytically through an alternative form of the Biot model, classically devoted to porous plates, and considering energy dissipation through viscous friction mechanisms. Analytical results are compared to experimental measurements of structural damping factors on various MPP samples. The model is validated and confirms the damping effect added by the microperforations in the low frequency range. A sensitivity analysis on the perforation rate and perforation diameter provides a condition for which additional damping is maximized.

In the context of structural dynamics, recent works by the authors showed that microperforations can be used to mitigate vibration. Microperforated plates (MPPs) have been shown to exhibit substantial added damping stemming from fluid-structure interactions and visco-thermal effect mechanisms in the boundary layers of the perforations during relative motion between the solid and the fluid contained in the perforations. The added damping reaches a maximum for a characteristic frequency, depending only on the perforation diameter. Choosing the perforation diameter so that the characteristic frequency coincides with the natural frequency of the plate reduces the mode contribution of the plate. However, the studied MPPs had a single set of perforations homogeneously distributed over the structure. It is proposed in this work to broaden the frequency band and maximize the added damping using MPPs with multi-sized perforation diameters and optimized spatial distribution of perforations. As an extension of the previous vibratory model by the author, the dynamics of MPPs with multi-sized perforation based on a homogenization model is established. In addition, the effect of the spacial distribution of perforations on the additional damping is captured by including a spatially dependent perforation ratio in the model. Experimental measurements on MPPs validate the proposed analytical models. The results show that: (i) MPPs with multiple size perforations exhibit a broader effective damping frequency band; (ii) the added damping enhances when the perforations are distributed in the area of the antinodes of the considered mode. Thus, by coupling the two effects, it is possible to achieve MPPs that effectively reduce the vibratory responses on several modes.

Increasing the damping properties of a structure while limiting the addition of mass is a challenging task. Originally developed for their acoustic absorption capabilities, microperforated plates (MPP) are simple devices that can feature additional viscous damping at low frequencies. Dissipation arises in the boundary layers of the microperforations through viscous friction mechanisms induced by the relative motion between the solid and the fluid in which the MPP is immersed. This leads to sound absorption in an acoustic context and to an added viscous damping in a solid dynamics context. The added viscous damping exhibited by the MPP can be captured by considering adapted fluid-solid interaction terms in the governing equations. A model was experimentally validated in a linear context. However, when the fluid velocity in the microperforations becomes sufficiently large, the inertial effects occurring in the microperforations can also have a significant impact. These are captured by Forchheimer's correction. Introducing this correction into the MPP linear vibration model leads to a nonlinear system with an additional antisymmetric quadratic damping term. The resulting equations of motion are solved numerically for a large amplitude forcing and quantitative analyses are performed. It is shown that the influence of antisymmetric quadratic nonlinear damping on the added viscous damping at the MPP depends on the magnitude of the external mechanical force. The model suggests the existence of maximum added viscous damping as a function of the external mechanical force magnitude.

In murine peritoneal and other serous cavities, Gata6 drives identity of the major resident cavity macrophage population, with a smaller subset of cavity macrophages dependent upon Irf4. Here we show that Gata6+ macrophages in the human peritoneum are rare, regardless of age. Instead, many aligned with CD206+LYVE1+ mouse cavity macrophages from a differentiation stage just preceding expression of Gata6. The comparatively low abundance of CD206+ converting macrophages in healthy C57BL/6J mice was sustained after high-fat diet feeding or in mice capture from the wild, suggesting that the major resident macrophages between the species share overlapping differentiation programs but differing predispositions to distinct differentiation stages. Irf4-dependent mouse serous cavity macrophages aligned closely with CD1c+CD14+CD64+ human peritoneal dendritic cells (DCs) that, in turn, resembled CD1c+CD14-CD64- peritoneal cDC2. Peritoneal DC1 and plasmacytoid DCs were rare in both species. This cross-species resource comparing mouse and human serous cavity immune cells will facilitate translational research.

Les plaques microperforées sont utilisées dans l’industrie pour leurs propriétés d’absorption acoustique. Ces structures légères, de par des échanges dans les couches limites visqueuses et thermiques près de l’interface fluide-structure, permettent l’absorption des ondes acoustiques. Il est montré dans ce travail que ces structures peuvent également induire un amortissement supplémentaire significatif particulièrement pour les basses fréquences. Ces solutions sans ajout de masse peuvent être un complément ou une alternative aux matériaux viscoélastiques couramment utilisés pour amortir les vibrations en moyennes et hautes fréquences.Ainsi il est proposé dans ce projet d’étudier les effets des microperforations sur l’amortissement des plaques finies. Pour cela, un modèle analytique basé sur une approche vibratoire de plaques poreuses finies est proposé. Des études paramétriques mettent en évidence l’existence d’une fréquence caractéristique qui lorsqu’elle coïncide avec un mode de plaque permet d’obtenir un amortissement ajouté maximal autour de ce mode. Cette fréquence est fonction des paramètres géométriques des microperforations. Des mesures vibratoires sur des plaques finies avec et sans microperforations permettent de valider le modèle et de confirmer ainsi l’effet d’amortissement ajouté par les microperforations en basses fréquences.

Background and ObjectivesChimeric antigen receptor (CAR) T-cell therapies have dramatically improved the prognosis of patients with relapsed or refractory hematologic malignancies; however, cytokine release syndrome and immune effector cell–associated neurotoxicity syndrome (ICANS) occur in ∼100 and 50% of patients, respectively. This study aimed to determine whether EEG patterns may be considered as diagnostic tools for ICANS.MethodsPatients who received CAR T-cell therapy at Montpellier University Hospital between September 2020 and July 2021 were prospectively enrolled. Neurologic signs/symptoms and laboratory parameters were monitored daily for 14 days after CAR T-cell infusion. EEG and brain MRI were performed between day 6 and 8 after CAR T-cell infusion. EEG was performed again on the day of ICANS occurrence, if outside this time window. All collected data were compared between patients with and without ICANS.ResultsThirty-eight consecutive patients were enrolled (14 women; median age: 65 years, interquartile range: [55–74]). ICANS was observed in 17 of 38 patients (44%) after a median time of 6 days after CAR T-cell infusion (4–8). The median ICANS grade was 2 (1–3). Higher C-reactive protein peak (146 mg/L [86–256],p= 0.004) at day 4 (3–6), lower natremia (131 mmol/L [129–132],p= 0.005) at day 5 (3–6), and frontal intermittent rhythmic delta activity (FIRDA,p< 0.001) on EEG between days 6 and 8 after infusion were correlated with ICANS occurrence. FIRDA was only observed in patients with ICANS (N = 15/17, sensitivity of 88%) and disappeared after ICANS resolution, usually after steroid therapy. Except for hyponatremia, no other toxic/metabolic marker was associated with FIRDA (p= 0.002). The plasma concentration of copeptin, a surrogate marker of antidiuretic hormone secretion, assessed at day 7 after infusion, was significantly higher in patients with (N = 8) than without (N = 6) ICANS (p= 0.043).DiscussionFIRDA is a reliable diagnostic tool for ICANS, with a sensitivity of 88% and a negative predictive value of 100%. Moreover, as this EEG pattern disappeared concomitantly with ICANS resolution, FIRDA could be used to monitor neurotoxicity. Finally, our study suggests a pathogenic pathway that starts with increased C-reactive protein, followed by hyponatremia and eventually ICANS and FIRDA. More studies are required to confirm our results.Classification of EvidenceThis study provides Class III evidence that FIRDA on spot EEG accurately distinguishes patients with ICANS compared with those without after CAR T-cell therapy for hematologic malignancy.

Brown adipose tissue (BAT) contains many immune cells. The presence of macrophages, monocytes, dendritic cells, T cells, B cells, and mast cells was documented in BAT. However, in comparison to white adipose tissue, relatively little is known on the impact of immune cells on BAT function. By directly interacting with BAT stromal cells, or by secreting pro- and anti-inflammatory mediators, immune cells modulate BAT activation and subsequently influence on adaptative thermogenesis and heat generation. In the current manuscript, we will focus on the diversity and functions of BAT immune cells.

Macrophages rely on tightly integrated metabolic rewiring to clear dying neighboring cells by efferocytosis during homeostasis and disease. Here we reveal that glutaminase-1-mediated glutaminolysis is critical to promote apoptotic cell clearance by macrophages during homeostasis in mice. In addition, impaired macrophage glutaminolysis exacerbates atherosclerosis, a condition during which, efficient apoptotic cell debris clearance is critical to limit disease progression. Glutaminase-1 expression strongly correlates with atherosclerotic plaque necrosis in patients with cardiovascular diseases. High-throughput transcriptional and metabolic profiling reveals that macrophage efferocytic capacity relies on a non-canonical transaminase pathway, independent from the traditional requirement of glutamate dehydrogenase to fuel ɑ-ketoglutarate-dependent immunometabolism. This pathway is necessary to meet the unique requirements of efferocytosis for cellular detoxification and high-energy cytoskeletal rearrangements. Thus, we uncover a role for non-canonical glutamine metabolism for efficient clearance of dying cells and maintenance of tissue homeostasis during health and disease in mouse and humans. Merlin et al. find that non-canonical glutamine transamination is required for macrophage efferocytosis in atherosclerotic plaques by sustaining redox buffering and fueling energy production for cytoskeletal rearrangements.

International audience; Metabolism plays a key role in controlling immune cell functions. In this review, we will discuss the diversity of plaque resident myeloid cells and will focus on their metabolic demands that could reflect on their particular intraplaque localization. Defining the metabolic configuration of plaque resident myeloid cells according to their topologic distribution could provide answers to key questions regarding their functions and contribution to disease development.

Introduction : Pour comprendre la politique de mise en œuvre de la refonte des vigilances, il etait utile de rappeler l’histoire du drame du sang contamine, element fondateur des nouvelles institutions sanitaires. Le concept de securite sanitaire est ne avec la creation de plusieurs agences nationales. Elles ont fait la preuve de leur utilite, mais restent, cependant, cloisonnees, avec un maillage territorial complexe constituant un frein a la declaration des evenements indesirables.Methode : Il a ete procede a une revue des textes de lois et de la litterature, depuis la crise du sang contamine jusqu’aux nouveaux textes relatifs a la reforme des vigilances.Resultats : L’hemovigilance et la creation de l’Etablissement Francais du Sang, operateur civil unique de la transfusion sanguine, ont ete des evolutions majeures dans la reduction des risques transfusionnels. Le Centre de Transfusion Sanguine des Armees, cree en 1945, est soumis aux memes exigences reglementaires. La fusion de plusieurs agences a permis une approche plus globale de l’evaluation des risques sanitaires et une protection plus efficace de la sante des populations.Discussion : Les structures sanitaires mises en place, depuis les drames sanitaires des annees 90, ont fait la preuve de leur utilite mais restent cependant avec une organisation qui s’appuie sur des agences distinctes quelquefois cloisonnees. La culture du signalement insuffisamment developpee est en train d’evoluer avec la mise en œuvre du portail national unique de signalement.Conclusion : On doit maintenant se preparer, en permanence, a des menaces nouvelles ou re-emergentes. Le risque lie a l’augmentation de l’exposition aux polluants et aux produits toxiques sera l’enjeu majeur des annees a venir.

Macrophages play a central role during infection, inflammation and tissue homeostasis maintenance. Macrophages have been identified in all organs and their core transcriptomic signature and functions differ from one tissue to another. Interestingly, macrophages have also been identified in the peritoneal cavity and these cells have been extensively used as a model for phagocytosis, efferocytosis and polarization. Peritoneal macrophages are involved in B-cell IgA production, control of inflammation and wound healing following thermal-induced liver surface injury. These cells presumably require and interact with the omentum, where milky spot stromal cells have been proposed to secrete CSF1 (colony stimulating factor 1). Peritoneal macrophages depend on CSF1 for their generation and survival, but the identity of CSF1 producing cells inside the large peritoneal cavity remains unknown. Here we investigated peritoneal macrophage localization and their interaction with mesothelial cells, the major cell type predicted to secrete CSF1. Our data revealed that mesothelial cells produce membrane bound and secreted CSF1 that both sustain peritoneal macrophage growth.

Macrophages are found across all organs in the body and play key roles in health and disease. Systemic stress is a major risk factor for a variety of chronic inflammatory diseases. However, the primary source for stress hormones, the adrenal gland (AGs), have yet to be thoroughly assessed for immune cell diversity. Here we utilized single cell RNA-sequencing (scRNA-seq) to investigate macrophage heterogeneity in nascent AGs, compared against acute stress (cold challenge) or a chronic stress model of cardiovascular disease. In steady state, we observed two major macrophage populations in the AG. Following acute and chronic stress, AG macrophages upregulated expression of inflammatory cytokines (Il1b, TNFa) and key lipid uptake molecules, including Trem2. These observations were replicated using imaging analysis showing hormone uptake by AG macrophages. Using a monocyte-fate-mapping approach, we observed increased recruitment following stressed conditions, which correlated with reduced AG macrophage proliferation. Finally, we observed exacerbated systemic corticosterone levels following AG macrophage depletion and Trem2 deficiency. Overall, these data define AG macrophage heterogeneity and suggest a regulatory function of AG macrophage following exposure to acute and chronic stress.

Inflammasomes are signalling platforms that are assembled in response to infection or sterile inflammation by cytosolic pattern recognition receptors. The consequent inflammasome-triggered caspase-1 activation is critical for the host defence against pathogens. During infection, NLRP3, which is a pattern recognition receptor that is also known as cryopyrin, triggers the assembly of the inflammasome-activating caspase-1 through the recruitment of ASC and Nek7. The activation of the NLRP3 inflammasome is tightly controlled both transcriptionally and post-translationally. Despite the importance of the NLRP3 inflammasome regulation in autoinflammatory and infectious diseases, little is known about the mechanism controlling the activation of NLRP3 and the upstream signalling that regulates the NLRP3 inflammasome assembly. We have previously shown that the Rho-GTPase-activating toxin from Escherichia coli cytotoxic necrotizing factor-1 (CNF1) activates caspase-1, but the upstream mechanism is unclear. Here, we provide evidence of the role of the NLRP3 inflammasome in sensing the activity of bacterial toxins and virulence factors that activate host Rho GTPases. We demonstrate that this activation relies on the monitoring of the toxin’s activity on the Rho GTPase Rac2. We also show that the NLRP3 inflammasome is activated by a signalling cascade that involves the p21-activated kinases 1 and 2 (Pak1/2) and the Pak1-mediated phosphorylation of Thr 659 of NLRP3, which is necessary for the NLRP3–Nek7 interaction, inflammasome activation and IL-1β cytokine maturation. Furthermore, inhibition of the Pak–NLRP3 axis decreases the bacterial clearance of CNF1-expressing UTI89 E. coli during bacteraemia in mice. Taken together, our results establish that Pak1 and Pak2 are critical regulators of the NLRP3 inflammasome and reveal the role of the Pak–NLRP3 signalling axis in vivo during bacteraemia in mice. Here, the authors present the upstream pathway that controls the activation of the NLRP3 inflammasome during bacteraemia. The CNF1 toxin from Escherichia coli activates the Rho GTPase Rac2 and its activity is sensed by NLRP3, which is activated by a signalling cascade involving p21-activated kinases 1 and 2.

International audience; Along with respiratory tract disease per se, viral respiratory infections can also cause extrapulmonary complications with a potentially critical impact on health. In the present study, we used an experimental model of influenza A virus (IAV) infection to investigate the nature and outcome of the associated gut disorders. In IAV-infected mice, the signs of intestinal injury and inflammation, altered gene expression, and compromised intestinal barrier functions peaked on day 7 postinfection. As a likely result of bacterial component translocation, gene expression of inflammatory markers was upregulated in the liver. These changes occurred concomitantly with an alteration of the composition of the gut microbiota and with a decreased production of the fermentative, gut microbiota-derived products short-chain fatty acids (SCFAs). Gut inflammation and barrier dysfunction during influenza were not attributed to reduced food consumption, which caused in part gut dysbiosis. Treatment of IAV-infected mice with SCFAs was associated with an enhancement of intestinal barrier properties, as assessed by a reduction in the translocation of dextran and a decrease in inflammatory gene expression in the liver. Lastly, SCFA supplementation during influenza tended to reduce the translocation of the enteric pathogen Salmonella enterica serovar Typhimurium and to enhance the survival of doubly infected animals. Collectively, influenza virus infection can remotely impair the gut's barrier properties and trigger secondary enteric infections. The latter phenomenon can be partially countered by SCFA supplementation.

Lymphatic collecting vessels and lymph nodes are inevitably embedded in adipose tissue. The physiological significance of this observation remains still not elucidated. However, obesity is characterized by impaired lymphatic function and increased vessel permeability. Inversely, lymphatic dysfunction induces obesity in mice, suggesting a significant interplay between lymphatic vessels and the adipose tissue. Therefore, understanding factors leading to lymphatic dysfunction might open new therapeutic windows to prevent obesity and associated comorbidities. The first step in this process requires a precise and detailed visualization of the lymphatic network in healthy and inflamed adipose tissue. Here, we describe a rapid, inexpensive, and efficient method that allows to label and analyze lymphatic and blood vessels. This approach takes advantage of the skin-draining brachial lymph node localization within the subcutaneous adipose tissue. The lymphatic arborization of this tissue can be revealed by injecting fluorochrome-conjugated lectins subcutaneously. Moreover, the in vivo labeling approach provides a way to evaluate lymphatic vessel density and functions. Coupled to blood vessel, adipocyte and immune cell staining, the protocol allows for high-resolution mapping of the subcutaneous adipose tissue by 3D imaging.

Macrophages rely on tightly integrated metabolic rewiring to clear dying neighboring cells by efferocytosis during homeostasis and disease. Here, we reveal glutaminase (Gls) 1-mediated glutaminolysis is critical to promote apoptotic cell clearance by macrophages during homeostasis. In addition, impaired macrophage glutaminolysis exacerbated atherosclerosis, a condition during which efficient apoptotic cell debris clearance is critical to limit disease progression. Gls1 expression strongly correlated with atherosclerotic plaque necrosis in patients with cardiovascular diseases. High-throughput transcriptional and metabolic profiling revealed that macrophage efferocytic capacity rely on a non-canonical transaminase pathway, independent from the traditional requirement of glutamate dehydrogenase (Glud1) to fuel ɑ-ketogulatrate-dependent immunometabolism. This pathway was necessary to meet the unique requirements of efferocytosis for cellular detoxification and high energy cytoskeletal rearrangements. Thus, we uncovered a novel role for non-canonical glutamine metabolism for efficient clearance of dying cells and maintenance of tissue homeostasis during health and disease.

To understand the policy for the implementation of the overhaul of the vigilance, it was useful to recall the context by revisiting the literature and regulation related to health security and the tragedy of contaminated blood, which was the founding element of the new health institutions. The concept of health security was born with the creation of several national agencies. They have proved their usefulness but remain, however, compartmentalized with a division of competences, in terms of vigilance, distributed between several agencies, in a complex territorial mesh constituting a hindrance to the declaration of undesirable events.Review of legal texts and literature, from the crisis of contaminated blood followed by the creation of health safety laws, the creation of health safety agencies to the texts relating to the reform of vigilance.Haemovigilance and the creation of the French Blood Establishment, the sole operator of blood transfusions, have been decisive in reducing transfusion chain accidents and the risks associated with infectious diseases. The merging of several agencies has led to a more comprehensive approach to risk assessment related to exposure to contaminants and more effective protection of the health of populations. At the regional level the management of sanitary vigilance at the ARS is well established and contributes locally to the management of alerts and health crises.The sanitary structures put in place have proved their usefulness but that is not enough. The culture of health events reporting that is insufficiently developed is changing with the implementation of the unique national portal for reporting and the development of health democracy.In addition, we must constantly prepare ourselves for new or re-emerging threats. The health risk linked to the foreseeable increase in exposure to pollutants and toxic products will be the major challenge for the years to come.