Dynamics of dendritic cell-T cell interactions: a role in T cell outcome

Antigen-specific dendritic cells (DC)-T cell encounters occur in lymph nodes (LNs) and are essential for the induction of both priming and tolerance. In both cases, T cells are rapidly activated and proliferate. However, the subsequent outcome of T cell activation depends on the modulation of different DC- and T cell-intrinsic signals. Recent advances in two-photon (2P) microscopy have furthered our understanding regarding the complex choreography of DCs and T cells in intact LNs, and established differences in the dynamics of DC-T cell contacts during priming and tolerance induction. The mechanisms that favour DC-T cell encounters, as well as the contribution of the frequency and the duration of such encounters in dictating the T cell response, are discussed in this revie

Risk Reduction Practices in Men Who Have Sex with Men in Switzerland: Serosorting, Strategic Positioning, and Withdrawal Before Ejaculation

The aim of this study was to identify predictors of intentional use of the HIV risk reduction practices of serosorting, strategic positioning, and withdrawal before ejaculation during unprotected anal intercourse (UAI) with casual partners. A cross-sectional survey pertaining to the Swiss HIV behavioral surveillance system, using an anonymous self-administered questionnaire, was conducted in 2007 in a self-selected sample of men having sex with other men (MSM). Analysis was restricted to participants with UAI with casual partner(s) (N=410). Logistic regression was used to estimate factors associated with intentional use of serosorting, strategic positioning, and withdrawal before ejaculation. In the previous 12months, 71% of participants reported having UAI with a casual partner of different or unknown HIV-status. Of these, 47% reported practicing withdrawal, 38% serosorting, and 25% strategic positioning. In the 319 participants with known HIV-status, serosorting was associated with frequent Internet use to find partners (OR=2.32), STI (OR=2.07), and HIV testing in the past 12months (OR=1.81). Strategic positioning was associated with HIV-status (OR=0.13) and having UAI with a partner of different or unknown HIV-status (OR=3.57). Withdrawal was more frequently practiced by HIV-negative participants or participants reporting high numbers of sexual partners (OR=2.48) and having UAI with a partner of unknown or different serostatus (OR=2.08). Risk reduction practices are widely used by MSM, each practice having its own specificities. Further research is needed to determine the contextual factors surrounding harm reduction practices, particularly the strategic or opportunistic nature of their us

Association between altered placental human chorionic gonadotrophin (hCG) production and the occurrence of cryptorchidism: a retrospective study

BACKGROUND: An increase in cryptorchidism has been reported in many countries. One mechanism could be low fetal testosterone production possibly secondary to altered placental human chorionic gonadotrophin (hCG) release. Our Objective was to compare hCG values from maternal blood between boys with cryptorchidism and normal boys. METHODS: Total hCG and α-fetoprotein (AFP) values [12–16 weeks of gestation; from the double test for Down syndrome screening) were compared between cases of cryptorchidism and normal control boys who were matched for maternal age, maternal smoking, gestational age at time of hCG measurement (±1 day), birth weight and birth term. Measurements were performed in a single laboratory; values were expressed as absolute values (KU/L) and multiples of the median (MoM). Boys whose mothers had had a complicated pregnancy were excluded. Groups were compared using the Student’s t test. Log transformation was used to normalize hCG, MoM hCG, AFP and MoM AFP distribution, and values were expressed as geometric means (-1, + 1 tolerance factor). RESULTS: Total hCG and MoM hCG levels were significantly lower in the 51 boys with cryptorchidism compared to 306 controls (21.4 (12.3; 37) KU/L vs 27.7 (15.9; 47.9) KU/L and 0.8 (0.5; 1.2) MoM vs 1.0 (0.6; 1.6) MoM, respectively, p < 0.01). By contrast, AFP and MoM AFP levels were similar between groups. CONCLUSION: This study showed a link between low maternal serum hCG levels and cryptorchidism in boys from uncomplicated pregnancy, while normal AFP levels indicated a normal fetoplacental unit. Whether these abnormalities were due to endogenous or exogenous factors remains to be determined

In vivo imaging of cytotoxic T cell infiltration and elimination of a solid tumor

Although the immune system evolved to fight infections, it may also attack and destroy solid tumors. In most cases, tumor rejection is initiated by CD8+ cytotoxic T lymphocytes (CTLs), which infiltrate solid tumors, recognize tumor antigens, and kill tumor cells. We use a combination of two-photon intravital microscopy and immunofluorescence on ordered sequential sections to analyze the infiltration and destruction of solid tumors by CTLs. We show that in the periphery of a thymoma growing subcutaneously, activated CTLs migrate with high instantaneous velocities. The CTLs arrest in close contact to tumor cells expressing their cognate antigen. In regions where most tumor cells are dead, CTLs resume migration, sometimes following collagen fibers or blood vessels. CTLs migrating along blood vessels preferentially adopt an elongated morphology. CTLs also infiltrate tumors in depth, but only when the tumor cells express the cognate CTL antigen. In tumors that do not express the cognate antigen, CTL infiltration is restricted to peripheral regions, and lymphocytes neither stop moving nor kill tumor cells. Antigen expression by tumor cells therefore determines both CTL motility within the tumor and profound tumor infiltration

Enseignement de l’ingénierie système : retour sur la conception d’un senseur stellaire pour ESEO et ESMO

Cet article présente la conception et le développement du logiciel embarqué d’un senseur stellaire, dans le cadre des projets étudiants de l’ESA (Agence Spatiale Européenne), tels ESEO (European Student Earth Orbiter) et ESMO (European Student Moon Orbiter). Ces projets sont menés au sein de l’ISAE (Institut Supérieur de l’Aéronautique et de l’Espace) par des élèves du cycle ingénieur de la formation SUPAERO, avec le soutien des équipes d’enseignants-chercheurs et des laboratoires de l’institut. Un senseur stellaire est un système complexe, composé d’une partie électronique, constituée de lentilles optiques, d’un déflecteur de lumière, d’un capteur, d’un micro-ordinateur et d’une partie logicielle comprenant les algorithmes de calcul et la base des données persistantes. Cet article se concentre sur l’application de la démarche d’ingénierie système, depuis le processus d’ingénierie du besoin jusqu’au processus d’architecture, permettant d’aboutir à une description physique de senseur stellaire

CD4+ T Cell Polarization in Mice Is Modulated by Strain-specific Major Histocompatibility Complex–independent Differences within Dendritic Cells

Resistance and susceptibility to Leishmania major in mice are determined by multiple genes and correlate with the preferential development of Th1 and Th2 responses, respectively. Here, we found that CD11b+ dendritic cells (DCs) prime parasite-specific CD4+ T cells in both susceptible BALB/c (H2-d) and resistant B10.D2 (H2-d) mice. However, BALB/c and B10.D2 DCs from L. major–infected mice differ in their ability to polarize naive T cells into Th1 or Th2 effector cells. This difference is cell-intrinsic, is not restricted to H2-d mice, and is observed with both parasite-specific and allospecific CD4+ T cells. Thus, strain-specific differences within CD11b+ DCs influence the ability of inbred mice to mount polarized CD4+ T cell responses

Border-Zone Cerebral Infarcts Associated with COVID-19 in CADASIL: A Report of 3 Cases and Literature Review

Introduction: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is the most common inherited cerebral small vessel disease and is a cause of early onset ischemic lacunar stroke. COVID-19 infection may lead, in addition to acute respiratory syndrome, to vascular complications including stroke. Herein, we report three CADASIL patients presenting with cerebral border-zone infarcts concomitant to COVID-19 infection and summarize similar cases previously published in literature. Methods: Clinical and radiological features of the 3 patients were collected and described. A narrative review of literature was performed in PubMed and Google Scholar by the end of 2022 using the “CADASIL” AND “COVID-19” AND “stroke” terms. Results: In our 3 patients, aged 40–58 years, stroke symptoms occurred one to 11 days after the first COVID-19 manifestations. Pulmonary symptoms were mild or absent. One patient presented with hemodynamic failure presumably related to acute cardiomyopathy. Brain magnetic resonance imaging revealed in all cases, ischemic lesions within border-zone areas in both cerebral hemispheres, lesions in the genu of the corpus callosum or in the medium cerebellar peduncles in two cases. The watershed pattern of ischemic lesions was detected in two cases despite any blood pressure drop or severe respiratory dysfunction. Seven CADASIL patients presenting with acute brain infarcts (multiple in 4/7) in context of SARS-CoV-2 infection were identified in literature, despite no fall in blood pressure except for one of them. Conclusion: Our observations, in line with previous reports, further suggest that COVID-19 infection may alter blood flow autoregulation in the deepest cerebral white matter in CADASIL patients. The thrombocytopathy and endotheliopathy developing during COVID-19 infection may participate to the underlying vascular processes

MHC class II-restricted antigen presentation by plasmacytoid dendritic cells drives proatherogenic T cell immunity

Background—Plasmacytoid dendritic cells (pDCs) bridge innate and adaptive immune responses and are important regulators of immuno-inflammatory diseases. However, their role in atherosclerosis remains elusive. Methods and Results—Here, we used genetic approaches to investigate the role of pDCs in atherosclerosis. Selective pDC deficiency in vivo was achieved using CD11c-Cre × Tcf4–/flox bone marrow transplanted into Ldlr–/– mice. Compared with control Ldlr–/– chimeric mice, CD11c-Cre × Tcf4–/flox mice had reduced atherosclerosis levels. To begin to understand the mechanisms by which pDCs regulate atherosclerosis, we studied chimeric Ldlr–/– mice with selective MHCII deficiency on pDCs. Significantly, these mice also developed reduced atherosclerosis compared with controls without reductions in pDC numbers or changes in conventional DCs. MHCII-deficient pDCs showed defective stimulation of apolipoprotein B100–specific CD4+ T cells in response to native low-density lipoprotein, whereas production of interferon-α was not affected. Finally, the atheroprotective effect of selective MHCII deficiency in pDCs was associated with significant reductions of proatherogenic T cell–derived interferon-γ and lesional T cell infiltration, and was abrogated in CD4+ T cell–depleted animals. Conclusions—This study supports a proatherogenic role for pDCs in murine atherosclerosis and identifies a critical role for MHCII-restricted antigen presentation by pDCs in driving proatherogenic T cell immunity

Pristine Mer de Corail: Les récifs éloignés de Nouvelle-Calédonie. Rapport au Gouvernement et aux trois Provinces de la Nouvelle-Calédonie,

Ce rapport scientifique présente un état des lieux des récifs éloignés de la Nouvelle-Calédonie mais aussi des récifs de l'ensemble des communes du pays, y compris en zones protégées. Une comparaison avec les récifs de 17 pays et territoires du Pacifique Insulaire, et avec les récifs parmi les plus riches de la planète, est également fournie. Un documentaire télévisuel de National Geographic à destination du grand public suit ce rapport

Macroautophagy in lymphatic endothelial cells inhibits T cell-mediated autoimmunity.

Lymphatic endothelial cells (LECs) present peripheral tissue antigens to induce T cell tolerance. In addition, LECs are the main source of sphingosine-1-phosphate (S1P), promoting naive T cell survival and effector T cell exit from lymph nodes (LNs). Autophagy is a physiological process essential for cellular homeostasis. We investigated whether autophagy in LECs modulates T cell activation in experimental arthritis. Whereas genetic abrogation of autophagy in LECs does not alter immune homeostasis, it induces alterations of the regulatory T cell (T reg cell) population in LNs from arthritic mice, which might be linked to MHCII-mediated antigen presentation by LECs. Furthermore, inflammation-induced autophagy in LECs promotes the degradation of Sphingosine kinase 1 (SphK1), resulting in decreased S1P production. Consequently, in arthritic mice lacking autophagy in LECs, pathogenic Th17 cell migration toward LEC-derived S1P gradients and egress from LNs are enhanced, as well as infiltration of inflamed joints, resulting in exacerbated arthritis. Our results highlight the autophagy pathway as an important regulator of LEC immunomodulatory functions in inflammatory conditions