Cell migration and antigen capture are antagonistic processes coupled by myosin II in dendritic cells

The immune response relies on the migration of leukocytes and on their ability to stop in precise anatomical locations to fulfil their task. How leukocyte migration and function are coordinated is unknown. Here we show that in immature dendritic cells, which patrol their environment by engulfing extracellular material, cell migration and antigen capture are antagonistic. This antagonism results from transient enrichment of myosin IIA at the cell front, which disrupts the back-to-front gradient of the motor protein, slowing down locomotion but promoting antigen capture. We further highlight that myosin IIA enrichment at the cell front requires the MHC class II-associated invariant chain (Ii). Thus, by controlling myosin IIA localization, Ii imposes on dendritic cells an intermittent antigen capture behaviour that might facilitate environment patrolling. We propose that the requirement for myosin II in both cell migration and specific cell functions may provide a general mechanism for their coordination in time and space

La migration cellulaire et la capture d'antigènes sont des fonctions antagonistes couplées par la Myosine II dans les cellules dendritiques

Les cellules dendritiques (DCs) patrouillent les tissus périphériques à la recherche de dangers potentiels en se déplaçant à travers les tissus et en incorporant de grande quantité de matériel extracellulaire. Cet événement précoce de la réponse immunitaire adaptative est susceptible de déterminer l'amplitude et la qualité de l'activation des lymphocytes T et B. De ce fait, les DCs pourraient avoir besoin d'orchestrer leur motilité et leur fonction de capture des antigènes afin d'initier un réponse immunitaire efficace et adaptée. Afin d'étudier les mécanismes responsables de l'optimisation de l'échantillonnage des tissus par les DCs, nous avons suivi leur migration et leur capacité à capturer des antigènes dans des chambres micro-fluidiques contenant des canaux étroits qui permettent de reproduire l'espace confiné des tissus périphériques. De manière surprenante, nous avons découvert que la migration des DCs et leur aptitude à accumuler des antigènes sont des fonctions antagonistes et dépendent de l'activité du moteur moléculaire Myosine II. Nous avons observé que les DCs se déplacent en alternant des phases rapides au cours desquelles la Myosine II est distribuée de manière asymétrique à l'arrière des cellules, et des phases plus lentes pendant lesquelles la Myosine II est enrichie à l'avant. Les enrichissements transitoires de Myosine II à l'avant des DCs dépendent de l'association de la Myosine II avec la chaîne invariante associée au CMH-II (Ii). Ces évenements favorisent l'absorption d'antigènes et leur transport dans les compartiments endolysosomaux. Des expériences menées avec une pince optique nous ont permis de montrer que l'activité de la Myosine II à l'avant des cellules génère des forces mécaniques qui induisent le transport des vésicules vers l'intérieur de la cellule, probablement en modulant le flux rétrograde d'actine. Ainsi, au cours de cette thèse, nous avons montré que la Myosine II était nécessaire à la fois pour la migration cellulaire et la capture d'antigènes, établissant un mécanisme moléculaire qui permet de coordonner ces deux processus dans le temps et l'espace. Nous proposons que l'alternance de phases de haute mobilité et de phases d'arrêt associées à la capture d'antigènes confère aux DCs une stratégie de recherche intermittente qui leur permettrait d'optimiser la surveillance des tissus périphériques.Dendritic cells (DCs) patrol peripheral tissues in search for potential dangers by actively crawling and internalizing extracellular materiel. This initial event of an adaptive immune response is likely to determine the magnitude and quality of T cell and B cell immunity. Therefore, DCs might need to tightly orchestrate their migration and their antigen uptake function in order to mount an efficient and adapted immune response. To investigate the mechanisms responsible for the optimization of tissues sampling by DCs, we monitored their migration and their ability to capture antigens in micro-fluidic chambers containing narrow channels that mimic the confined space of peripheral tissues. Surprisingly, we found that cell migration and antigen accumulation in endolysosomes are antagonistic, both relying on the activity of the motor protein Myosin II. We observed that DCs alternate between phases of fast motility during which Myosin II is asymmetrically distributed at the cell rear, and phases of slow motility during which Myosin is enriched at the cell front. Transient Myosin II enrichments at the leading edge depends on its association with the MHC-II associated Invariant Chain (Ii). These events promote antigen uptake and arrival in endolysosomal compartments. Using optical tweezers, we further showed that Myosin II activity at the leading edge generates mechanical forces that drive vesicles transport toward the cell body probably through the modulation of F-actin retrograde flow. Thus, during my PhD, we have shown that Myosin II is required for both migration and antigen capture, providing a molecular mechanism to couple these two processes and allow their coordination in time and space. We propose that alternation between phases of fast motility and phases of low motility associated with efficient antigen capture imposes an intermittent search behavior on DCs, which might be optimal for environment patrolling

Infection-on-Chip: an in vitro human vessel to study Neisseria meningitidis colonization and vascular damages

Abstract Bloodstream infections leading to sepsis are a life-threatening condition and remain difficult to treat, however, in vitro experimental models that reflect their key features are still lacking. We here developed a photoablation-based 3-dimensional, microfluidic model of meningococcal vascular colonization, which allows to study cardinal features of the bacteria-blood vessel interaction within controllable vascular geometries. Meningococci are Gram-negative human-specific bacteria responsible for meningitis and a severe form of sepsis that is associated with vascular damages, referred to as purpura fulminans . The infection-on-chip device is used to quantitatively assess bacterial adhesion and proliferation at high spatio-temporal resolution in a physiologically relevant microenvironment. In addition, we here show that vascular colonization by meningococci in our Infection-on-Chip device recapitulates key features of disease progression, including vascular leakage and the recruitment of neutrophils to sites of infections, mirroring results obtained using our previously described human skin xenograft mouse model. As a result, our Infection-on-chip platform provides a robust alternative approach to the use of animal and 2D cellular models, opening the path to the better understanding of disease progression and testing innovative therapeutics in an in vitro but physiologically relevant environment

Contour current imprints and contourite drifts in the Bahamian archipelago

International audienc

CD146 at the Interface between Oxidative Stress and the Wnt Signaling Pathway in Systemic Sclerosis

International audienc

CD36-specific antibodies block release of HIV-1 from infected primary macrophages and its transmission to T cells

International audienceHIV-1-infected macrophages likely represent viral reservoirs, as they accumulate newly formed virions in internal virus-containing compartments (VCCs). However, the nature and biogenesis of VCCs remain poorly defined. We show that upon HIV-1 infection of primary human macrophages, Gag is recruited to preexisting compartments containing the scavenger receptor CD36, which then become VCCs. Silencing of CD36 in HIV-1-infected macrophages decreases the amount of virions released. Strikingly, soluble anti-CD36 antibodies, but not the natural ligands of CD36, inhibit release of virions from HIV-1-infected macrophages and the transmission of virus to CD4(+) T cells. The effect of the antibodies is potent, rapid, and induces the retention of virions within VCCs. Ectopic expression of CD36 in HeLa cells renders them susceptible to the inhibitory effect of the anti-CD36 mAb upon HIV-1 infection. We show that the anti-CD36 mAb inhibits HIV-1 release by clustering newly formed virions at their site of budding, and that signaling via CD36 is not required. Thus, HIV-1 reservoirs in macrophages may be tackled therapeutically using anti-CD36 antibodies to prevent viral dissemination

Práticas econômicas e formas ordinárias de cálculo

Este artigo parte da hipótese da existência de uma pluralidade de cenas sociais em que os indivíduos interagem e as ações individuais adquirem sentido. A cada cena social correspondem racionalidades práticas diferentes. O exame das práticas de mensuração e contabilidade permite distinguir essas cenas e compreender como se articulam entre si. Para mostrar a diversidade de raciocínios nativos, utiliza-se primeiro a diversidade das unidades de medida usadas por horticultores amadores. Em seguida, examinam-se os quadros rituais de diversas transações e mostra-se que o consumidor racional &shy; no sentido da teoria utilitarista &shy; pode não recorrer a nenhum cálculo explícito, pois o ethos ascético encontra-se inscrito nas rotinas corporais. Para concluir, o artigo convida a um estudo sistemático da socialização econômica e propõe três pistas para a pesquisa: a descrição da diversidade de cenas sociais, a análise dos quadros rituais das transações, e o estudo das percepções dos constrangimentos e das práticas de autocontrole nas diversas classes sociais. O artigo sugere que, dessa forma, se poderiam definir domínios de validade para as formalizações matemáticas das condutas humanas elaboradas pelos economistas.<br>This article proceeds from the hypothesis that a plurality of social scenes exist in which individuals interact and individual actions acquire meaning. Each social scene corresponds to different practical rationalities. Examining the practices involved in measuring and counting allows us to distinguish these scenes and comprehend how they are mutually interconnected. As a demonstration of the diversity of native reasoning, the article first turns to the wide variety of units of measurement used by amateur horticulturists. Next, it examines the ritual settings of various transactions and shows that the rational consumer &shy; in the sense expounded by utilitarian theory &shy; need not rely on any explicit calculation, since the ascetic ethos can be found inscribed in body routines. In conclusion, the article calls for a systematic study of economic socialization and outlines three leads for such research: description of the diversity of social scenes, analysis of the ritual settings of transactions, and study of the perceptions of constraints and the practices of self-control among the various social classes. The author suggests such an approach may enable us to define domains of validity for the mathematical formalizations of human behaviours developed by economists

Antibiotiques et résistance bactérienne : pistes d'actions pour ancrer les progrès de 2020

International audienceL'année 2020 a bouleversé les comportements du quotidien, en raison de la pandémie de COVID-19 et des confinements et gestes barrières à adopter pour limiter sa propagation. Ces modifications ont contribué à limiter la transmission des autres infections ; elles ont aussi impacté le recours aux soins et la prise en charge de certaines pathologies en santé humaine