Immunopathologie de la leptospirose humaine : exploration de la réponse immunitaire innée.

Leptospirosis is a bacterial zoonosis caused by Leptospira and affecting 1 million people each year worldwide and mainly in tropical areas such as Reunion Island. Usual presentations encompass flu-like syndrome to multiorgan failure with mortality rate between 5 to 10%. To date, pathophysiology in humans is poorly understood, notably the capacity of innateimmunity to mount a robust response to clear pathogen or to induce tissue damages and contributing to disease severity. Our study aimed at assessing the role of innate immune cells and molecules within the first days of leptospiral infection.Using blood samples, we performed quantitative and qualitative assessment of circulating innate immune cells from leptospirosis cases and healthy controls. The first study explored the levels of gamma-delta T-cells (γδT-cells), a subset of unconventional T cells with innate immune functions. Gamma-delta T cells were found deeply decreased and levels wereinversely correlated to bacterial burden and liver damage. The second study focused on membrane bound receptors indicative of activation and tissue migration ability of neutrophil polymorphonuclear cells: CD15, CD11b, and CD182. Although neutrophil rates were high in leptospirosis cases, the levels of studied receptors were either lower (CD15) or identical to healthy controls (CD11b, CD182). In addition, only low levels of interleukin-8, a key chemokine for neutrophils, was detected in patients. Lastly, we ascertained the plasmatic levels of several shed cell adhesion molecules notably expressed by endothelial cells. The levels of soluble E-selectin and ICAM-1 were significantly increased compared to controls, while P-selectin level was lower. We did not find any correlation with disease severity or organ failure. This finding indicates that endothelial cell may be activated but further experiments are warranted to explain the functional impact of our findings. Altogether, our results add to the field of knowledge of leptospirosis pathophysiology, and in particular the implication of key innate immune cells at the stage of plasmatic bacterial dissemination. Our findings will support the view that there is an inappropriate immune response to Leptospira.La leptospirose est une zoonose causée par les bactéries du genre Leptospira. Elle touche près de 1 million d'individus par an dans le monde entier et sévit à l'état endémique dans les pays au climat tropical tel que La Réunion. Les manifestations habituelles sont variables d'un individu à l'autre et englobent une simple fièvre jusqu'aux défaillances poly-viscérales avec mortalité dans 5 à 10% des cas. Sa physiopathologie est encore mal comprise, en particulier la part que joue une réponse immunitaire inappropriée dans la genèse des manifestations graves qui surviennent en quelques heures, et avant la mise en place d'une réponse immunitaire adaptative propre à éliminer le microorganisme. Si l'échappement de la bactérie au système du complément est bien documenté, le rôle des acteurs cellulaires du système immunitaire inné reste à étayer. Notre étude avait donc pour objectif d'explorer l'immunopathologie de la leptospirose humaine dans la phase initiale de l’infection. Notre méthodologie s'est appuyée principalement sur des analyses quantitatives et qualitatives des acteurs cellulaires du système immunitaire inné à partir de prélèvements sanguins en phase précoce de la maladie, et comparaison avec la phase de convalescence et des sujets contrôles. Dans un premier temps nous avons montré qu'une population particulière de lymphocytes T impliquée dans la réponse immune innée, les lymphocytes Tγδ, avaient un taux abaissé et que cette baisse était corrélée à la charge bactérienne ainsi qu'à l’intensité de l'atteinte hépatique classiquement retrouvée lors de la leptospirose. Dans un deuxième temps, nous avons analysé les polynucléaires neutrophiles circulants dont le taux augmente d’autant plus que la maladie est sévère, mais sans pour autant présenter de modification de certains marqueurs d’activation ou de recrutement tissulaire (CD15, CD11b, CD182). Une des principales chimiokines des neutrophiles, l'interleukine 8, était à taux peu élevés. Les derniers travaux concernent les principales formes solubles issues des molécules membranaires impliquées dans le processus de recrutement/diapédèse leucocytaire. Nous retrouvons de manière isolée une forte élévation des formes solubles d'E-sélectine et ICAM-1 qui sont notamment exprimées par les cellules endothéliales. Ces augmentations n'étaient pas corrélées aux marqueurs de gravité de la maladie. La signification biologique de cette élévation n’est pas encore connue lors de la leptospirose. L'ensemble de nos données permet d’apporter des informations nouvelles sur des acteurs du système immunitaire inné présents dans le compartiment vasculaire lors de la leptospirose humaine. Cette réponse immunitaire semble inadaptée pour permettre une clairance du pathogène au stade de dissémination hématogène

Local Structure and Dynamics of Lithium Garnet Ionic Conductors: A Model Material Li₅La₃Ta₂O₁₂

In this article, we combined two complementary structure/dynamics probes, i.e., total-scattering/reverse Monte Carlo (RMC) modeling and classical molecular dynamics (MD), in order to understand local lithium structure and dynamics in a model disordered garnet oxide Li₅La₃Ta₂O₁₂. By examining the configurations from RMC and trajectories from MD, we individually and statistically analyzed the lithium distribution and dynamics within tetrahedral (Td) cages, octahedral (Oh) cages, and triangular bottlenecks. We found that lithium atoms within either Td or Oh cages prefer to stay at the off-center positions and close to one of the triangular bottlenecks. This is likely caused by the uneven Li–Li interaction in the form of lithium clusters, and such geometrical frustration leads to the local structure instability and fast ionic conduction. Both RMC and MD studies support that the lithium conduction path goes through the triangular bottleneck in a 3D continuous network of Td/Oh cages, without a direct Oh to Oh jump. However, the conduction mechanism should not be generalized, as it is greatly influenced by the local environment or temperature. Broadly speaking, lithium atoms hop through the bottleneck from an edge-passing mechanism at low temperatures to a center-passing mechanism at higher temperatures

Excellent Bifunctional Oxygen Evolution and Reduction Electrocatalysts (5A_1/5)Co₂O₄ and Their Tunability

Hastening the progress of rechargeable metal–air batteries and hydrogen fuel cells necessitates the advancement of economically feasible, earth-abundant, inexpensive, and efficient electrocatalysts facilitating both the oxygen evolution reaction (OER) and oxygen reduction reaction (ORR). Herein, a recently reported family of nano (5A1/5)Co2O4 (A = combinations of transition metals, Mg, Mn, Fe, Ni, Cu, and Zn) compositionally complex oxides (CCOs) [Wang et al., Chemistry of Materials, 2023, 35 (17), 7283–7291.] are studied as bifunctional OER and ORR electrocatalysts. Among the different low-temperature soft-templating samples, those subjected to 600 °C postannealing heat treatment exhibit superior performance in alkaline media. One specific composition (Mn0.2Fe0.2Ni0.2Cu0.2Zn0.2)Co2O4 exhibited an exceptional overpotential (260 mV at 10 mA cm–2) for the OER, a favorable Tafel slope of 68 mV dec–1, excellent onset potential (0.9 V) for the ORR, and lower than 6% H2O2 yields over a potential range of 0.2 to 0.8 V vs the reversible hydrogen electrode. Furthermore, this catalyst displayed stability over a 22 h chronoamperometry measurement, as confirmed by X-ray photoelectron spectroscopy analysis. Considering the outstanding performance, the low cost and scalability of the synthesis method, and the demonstrated tunability through chemical substitutions and processing variables, CCO ACo2O4 spinel oxides are highly promising candidates for future sustainable electrocatalytic applications

Nanoscale Ni/Mn Ordering in the High Voltage Spinel Cathode LiNi_0.5Mn_1.5O₄

Nanoscale Ni/Mn Ordering in the High Voltage Spinel Cathode LiNi_0.5Mn_1.5O<sub>4</sub

Resolving the Structure of Ti₃C₂T_<i>x</i> MXenes through Multilevel Structural Modeling of the Atomic Pair Distribution Function

MXenes are a recently discovered family of two-dimensional (2D) early transition metal carbides and carbonitrides, which have already shown many attractive properties and great promise in energy storage and many other applications. However, a complex surface chemistry and small coherence length have been obstacles in some applications of MXenes, also limiting the accuracy of predictions of their properties. In this study, we describe and benchmark a novel way of modeling layered materials with real interfaces (diverse surface functional groups and stacking order between the adjacent monolayers) against experimental data. The structures of three kinds of Ti₃C₂T_<i>x</i> MXenes (T stands for surface terminating species, including O, OH, and F) produced under different synthesis conditions were resolved for the first time using atomic pair distribution function obtained by high-quality neutron total scattering. The true nature of the material can be easily captured with the sensitivity of neutron scattering to the surface species of interest and the detailed “third-generation” structure model we present. The modeling approach leads to new understanding of MXene structural properties and can replace the currently used idealized models in predictions of a variety of physical, chemical, and functional properties of Ti₃C₂-based MXenes. The developed models can be employed to guide the design of new MXene materials with selected surface termination and controlled contact angle, catalytic, optical, electrochemical, and other properties. We suggest that the multilevel structural modeling should form the basis for a generalized methodology on modeling diffraction and pair distribution function data for 2D and layered materials

Dependence of the Li-Ion Conductivity and Activation Energies on the Crystal Structure and Ionic Radii in Li₆MLa₂Ta₂O₁₂

Inspired by the promising ionic conductivities of the lithium conducting garnets, we present a comparative study on the influence of the ionic radius of M²⁺ on the 8-coordinate site and the crystal structure on the ionic transport in the solid solution Li₆MLa₂Ta₂O₁₂. Neutron diffraction and synchrotron diffraction in combination with AC impedance measurements are employed to understand the systematic substitution with different-sized alkaline earth cations M²⁺. As may be expected, the unit-cell parameters increase linearly with increasing ionic radius from Ca²⁺ over Sr²⁺ to Ba²⁺, accompanied by an increase in the polyhedral volumes of the dodecahedral, and tetrahedral positions and the ionic conductivities. While the TaO₆ octahedral volume remain constant, the anisotropic thermal parameters of the coordinating oxygen anions suggest a high degree of rotational freedom with increasing unit-cell size. These structural parameters lead to lower activation energies because of broader Li conduction pathways and a higher flexibility in the crystal lattice, ultimately controlling the ionic conductivities in this class of materials

Mesoporous RE_0.5Ce_0.5O_2–<i>x</i> Fluorite Electrocatalysts for the Oxygen Evolution Reaction

Developing highly active and stable electrocatalysts for the oxygen evolution reaction (OER) is key to improving the efficiency and practical application of various sustainable energy technologies including water electrolysis, CO2 reduction, and metal air batteries. Here, we use evaporation-induced self-assembly (EISA) to synthesize highly porous fluorite nanocatalysts with a high surface area. In this study, we demonstrate that a 50% rare-earth cation substitution for Ce in the CeO2 fluorite lattice improves the OER activity and stability by introducing oxygen vacancies into the host lattice, which results in a decrease in the adsorption energy of the OH* intermediate in the OER. Among the binary fluorite compositions investigated, Nd2Ce2O7 is shown to display the lowest OER overpotential of 243 mV, achieved at a current density of 10 mA cm–2, and excellent cycling stability in an alkaline medium. Importantly, we demonstrate that rare-earth oxide OER electrocatalysts with high activity and stability can be achieved using the EISA synthesis route without the incorporation of transition and noble metals

Uncovering the True Atomic Structure of Disordered Materials: The Structure of a Hydrated Amorphous Magnesium Carbonate (MgCO₃·3D₂O)

Amorphous calcium/magnesium carbonates are of significant interest in the technology sector for a range of processes, including carbon storage and biomineralization. Here, the atomic structure of one hydrated amorphous magnesium carbonate (hydrated AMC, MgCO₃·3D₂O) is investigated using an iterative methodology, where quantum chemistry and experimental total scattering data are combined in an interactive iterative manner to produce an experimentally valid structural representation that is thermodynamically stable. The atomic structure of this hydrated AMC consists of a distribution of Mg²⁺ coordination states, predominately V- and VI-fold, and is heterogeneous due to the presence of Mg²⁺/CO₃^2‑-rich regions interspersed with small ‘pores’ of water molecules. This heterogeneity at the atomic length scale is likely to contribute to the dehydration of hydrated AMC by providing a route for water molecules to be removed. We show that this iterative methodology enables wide sampling of the potential energy landscape, which is important for elucidating the true atomic structure of highly disordered metastable materials

Large-Scale Synthesis and Comprehensive Structure Study of δ‑MnO₂

Layered δ-MnO₂ (birnessites) are ubiquitous in nature and have also been reported to work as promising water oxidation catalysts or rechargeable alkali-ion battery cathodes when fabricated under appropriate conditions. Although tremendous effort has been spent on resolving the structure of natural/synthetic layered δ-MnO₂ in the last few decades, no conclusive result has been reached. In this Article, we report an environmentally friendly route to synthesizing homogeneous Cu-rich layered δ-MnO₂ nanoflowers in large scale. The local and average structure of synthetic Cu-rich layered δ-MnO₂ has been successfully resolved from combined Mn/Cu K-edge extended X-ray fine structure spectroscopy and X-ray and neutron total scattering analysis. It is found that appreciable amounts (∼8%) of Mn vacancies are present in the MnO₂ layer and Cu²⁺ occupies the interlayer sites above/below the vacant Mn sites. Effective hydrogen bonding among the interlayer water molecules and adjacent layer O ions has also been observed for the first time. These hydrogen bonds are found to play the key role in maintaining the intermediate and long-range stacking coherence of MnO₂ layers. Quantitative analysis of the turbostratic stacking disorder in this compound was achieved using a supercell approach coupled with anisotropic particle-size-effect modeling. The present method is expected to be generally applicable to the structural study of other technologically important nanomaterials