Contribution a l'etude moleculaire des glutathion S-transferases dans le cadre d'une strategie vaccinale contre les schistosomiases

SIGLEAvailable from INIST (FR), Document Supply Service, under shelf-number : T 84339 / INIST-CNRS - Institut de l'Information Scientifique et TechniqueFRFranc

Prostaglandin D2 affects the maturation of human monocyte-derived dendritic cells: consequence on the polarization of naive Th cells.

peer reviewedAmong the factors produced at inflammatory sites and those capable of modulating dendritic cell (DC) functions, PGD(2) may be important in the outcome of immune responses. The biological roles for PGD(2) are in part effected through two plasma membrane G protein-coupled receptors: the D prostanoid (DP) receptor and the chemoattractant receptor-homologous molecule expressed on Th2 lymphocytes (CRTH2). In this report, we studied the effects of PGD(2) and of its major physiological metabolite, 15-deoxy-Delta(12,14)-PGJ(2) (15d-PGJ(2)), on the functions of human monocyte-derived DC. First, we show that PGD(2) exerts in vitro chemotactic effects on monocytes via CRTH2 activation while it inhibits the chemokine-driven migration of monocyte-derived DC through DP. We also report that PGD(2) and 15d-PGJ(2) alter the LPS- and allergen-induced DC maturation and enhance the CD80/CD86 ratio on mature DC in a DP- and CRTH2-independent manner. Moreover, PGD(2) and 15d-PGJ(2) strongly reduce the secretion of the Th1 promoting cytokine IL-12 and affect the synthesis of chemokines involved in Th1 cell chemotaxis, particularly CXCL10. Inhibition of cytokine/chemokine secretion implicates at least in part DP, but not CRTH2. The effects exerted by PGD(2) are associated with the phosphorylation of CREB, but do not parallel with the deactivation of the NF-kappa B and mitogen-activated protein kinase pathways. In contrast, 15d-PGJ(2) seems to target other cellular proteins. Finally, in a model of Th CD45RA(+) differentiation induced by allergen- and superantigen-pulsed DC, PGD(2) impacts on the orientation of the immune response by favoring a Th2 respons

Schistosoma mansoni Activates Host Microvascular Endothelial Cells To Acquire an Anti-Inflammatory Phenotype

Since endothelial cells (ECs) play a key role in immune defense mechanisms and in immunopathology, we investigated whether the intravascular helminth parasite Schistosoma mansoni could interact with and activate resting ECs in vitro. Microscopic analysis revealed that the lung-stage schistosomula specifically attached to microvascular ECs. This adherence was associated to active cellular processes involving actin filament formation. Since variation of permeability of cultured capillary brain ECs is a good marker for endothelial activation, the transendothelial passage of a low-molecular-weight molecule (inulin) on monolayers of bovine brain capillary ECs (BBCEC) was measured in response to parasites. Schistosomula induced a dramatic decrease in transendothelial permeability, a characteristic marker for the generation of an anti-inflammatory phenotype to ECs. This paracellular barrier enhancing effect on endothelial monolayers was due to a soluble substance(s) (below 1 kDa in size) secreted from S. mansoni schistosomula and not by mechanisms associated to adherence between parasites and ECs. The reinforcement of the endothelial barrier function was accompanied by an elevation of intracellular concentration of cyclic AMP (cAMP). The use of specific kinase inhibitors confirms that schistosomula activate ECs through a cAMP/protein kinase A pathway that leads to an increased phosphorylation of the myosin light-chain kinase. These combined findings suggest that the secretory/excretory products from schistosomula possess anti-inflammatory factor(s) that signal host microvascular endothelium. The immunological consequences of such activation are discussed

Prostaglandin D2 inhibits the production of interleukin-12 in murine dendritic cells through multiple signaling pathways.

Prostaglandin (PG) D(2), and its metabolites, are known to be important mediators during acute and chronic inflammation. However, their functions during the early phases of the immune response are poorly documented. In the present study, we show that PGD(2 )inhibits, in a dose-dependent manner, the CD40- and LPS-induced secretion of the Th1-driving factor IL-12 by murine splenic dendritic cells (DC), the most potent antigen-presenting cells. The inhibition of IL-12 production is mediated only in part by the cell surface G alpha s protein-coupled D prostanoid receptor (termed DP1) but not by the G alpha i protein-coupled DP receptor, DP2. We show that recruitment of DP1 in DC results in the activation of a cyclic AMP/protein kinase A pathway that is partially responsible for the inhibition of IL-12 production. We also suggest that the DP1-independent effects exerted by PGD(2) on IL-12 production may be due to the action of ist PGJ(2), but not PGF(2)alpha, metabolites. Electrophoretic mobility shift assays demonstrated that PGD(2) affects NF-kappa B activation through (the) DP1-independent pathway(s). Together these data suggest that PGD(2), by interacting with DP1 and by binding to other target cellular proteins, may regulate immune responses by affecting IL-12 production in D

Pseudomonas aeruginosa proteolytically alters the interleukin 22-dependent lung mucosal defense

International audienceThe IL-22 signaling pathway is critical for regulating mucosal defense and limiting bacterial dissemination. IL-22 is unusual among interleukins because it does not directly regulate the function of conventional immune cells, but instead targets cells at outer body barriers, such as respiratory epithelial cells. Consequently, IL-22 signaling participates in the maintenance of the lung mucosal barrier by controlling cell proliferation and tissue repair, and enhancing the production of specific chemokines and anti-microbial peptides. Pseudomonas aeruginosa is a major pathogen of ventilator-associated pneumonia and causes considerable lung tissue damage. A feature underlying the pathogenicity of this bacterium is its capacity to persist and develop in the host, particularly in the clinical context of nosocomial lung infections. We aimed to investigate the ability of P. auruginosa to disrupt immune-epithelial cells cross-talk. We found that P. aeruginosa escapes the host mucosal defenses by degrading IL-22, leading to severe inhibition of IL-22-mediated immune responses. We demonstrated in vitro that, protease IV, a type 2 secretion system-dependent serine protease, is responsible for the degradation of IL-22 by P. aeruginosa. Moreover, the major anti-proteases molecules present in the lungs were unable to inhibit protease IV enzymatic activity. In addition, tracheal aspirates of patients infected by P. aeruginosa contain protease IV activity which further results in IL-22 degradation. This so far undescribed cleavage of IL-22 by a bacterial protease is likely to be an immune-evasion strategy that contributes to P. aeruginosa-triggered respiratory infections

CPCN - BILAN DE MANDATURE 2016 – 2021

Le présent bilan de mandature 2016-2021 de la CPCN (Conférence des présidentes et présidents de sections et de commissions interdisciplinaires du Comité national de la recherche scientifique) a une triple finalité. Il constitue d’abord une forme d’autoévaluation de l’action de la CPCN et, à travers elle, de l’action coordonnée des sections et commissions interdisciplinaires (CID), au cours de cette mandature, en rappelant autant que de besoin le contexte dans lequel cette action s’est inscrite. Il vise également à rendre compte de cette action auprès de la communauté scientifique française à travers une diffusion la plus large possible. Il doit enfin permettre un passage de relais avec les sections et CID et avec la CPCN qui seront mises en place à l’automne 2021