Genetic and environmental factors are critical elements influencing the etiology of major depression. It is now accepted that neuroinflammatory processes play a major role in neuropsychological disorders. Neuroinflammation results from the dysregulation of the synthesis and/or release of pro- and anti-inflammatory cytokines with central or peripheral origin after various insults. Systemic bacterial lipopolysaccharide (LPS) challenge is commonly used to study inflammation-induced depressive-like behaviors in rodents. In the present study, we investigated immune-to-brain communication in mice by examining the effects of peripheral LPS injection on neuroinflammation encompassing cytokine and chemokine production, microglia and central nervous system (CNS)-associated phagocyte activation, immune cell infiltration and serotonergic neuronal function.

Cutaneous squamous cell carcinoma (cSCC) development has been linked to immune dysfunctions but the mechanisms are still unclear. Here, we report a progressive infiltration of tumor-associated neutrophils (TANs) in precancerous and established cSCC lesions from chemically induced skin carcinogenesis. Comparative in-depth gene expression analyses identified a predominant protumor gene expression signature of TANs in lesions compared to their respective surrounding skin. In addition, in vivo depletion of neutrophils delayed tumor growth and significantly increased the frequency of proliferating IFN-γ (interferon-γ)-producing CD8+ T cells. Mechanisms that limited antitumor responses involved high arginase activity, production of reactive oxygen species (ROS) and nitrite (NO), and the expression of programmed death-ligand 1 (PD-L1) on TAN, concomitantly with an induction of PD-1 on CD8⁺ T cells, which correlated with tumor size. Our data highlight the relevance of targeting neutrophils and PD-L1-PD-1 (programmed death-1) interaction in the treatment of cSCC.

Perilipins (PLINs), the most abundant proteins on lipid droplets (LDs), display similar domain organization including amphipathic helices (AH). However, the five human PLINs bind different LDs, suggesting different modes of interaction. We established a minimal system whereby artificial LDs covered with defined polar lipids were transiently deformed to promote surface tension. Binding of purified PLIN3 and PLIN4 AH was strongly facilitated by tension but was poorly sensitive to phospholipid composition and to the presence of diacylglycerol. Accordingly, LD coverage by PLIN3 increased as phospholipid coverage decreased. In contrast, PLIN1 bound readily to LDs fully covered by phospholipids; PLIN2 showed an intermediate behavior between PLIN1 and PLIN3. In human adipocytes, PLIN3/4 were found in a soluble pool and relocated to LDs upon stimulation of fast triglyceride synthesis, whereas PLIN1 and PLIN2 localized to pre-existing LDs, consistent with the large difference in LD avidity observed in vitro. We conclude that the PLIN repertoire is adapted to handling LDs with different surface properties.

Reactive oxygen species such as hydrogen peroxide (H₂O₂) are key signaling molecules that control the setup and functioning of Rhizobium-legume symbiosis. This interaction results in the formation of a new organ, the root nodule, in which bacteria enter the host cells and differentiate into nitrogen (N₂)-fixing bacteroids. The interaction between Sinorhizobium meliloti and Medicago truncatula is a genetic model to study N₂-fixing symbiosis. In previous work, S. meliloti mutants impaired in the antioxidant defense, showed altered symbiotic properties, emphasizing the importance of redox-based regulation in the bacterial partner. However, direct measurements of S. meliloti intracellular redox state have never been performed. Here, we measured dynamic changes of intracellular H₂O₂ and glutathione redox potential by expressing roGFP2-Orp1 and Grx1-roGFP2 biosensors in S. meliloti. Kinetic analyses of redox changes under free-living conditions showed that these biosensors are suitable to monitor the bacterial redox state in real-time, after H₂O₂ challenge and in different genetic backgrounds. In planta, flow cytometry and confocal imaging experiments allowed the determination of sensor oxidation state in nodule bacteria. These cellular studies establish the existence of an oxidative shift in the redox status of S. meliloti during bacteroid differentiation. Our findings open up new possibilities for in vivo studies of redox dynamics during N₂-fixing symbiosis.

Ces dernières années ont vu une progression importante des capacités des nouveaux appareils de cytométrie. Deux sauts technologiques ont été récemment franchis avec la cytométrie couplée à la spectrométrie de masse, dans laquelle les fluorochromes ont été remplacés par des métaux rares non radioactifs de la famille des lanthanides et la cytométrie spectrale qui collecte les photons sur le spectre visible. Dans cette revue, nous décrivons schématiquement la cytométrie en flux conventionnelle et ces deux technologies ainsi que leurs avantages et adaptabilités et leurs inconvénients.