Role of Sex and Early Interferon Production in the Susceptibility of Mice to Encephalomyocarditis Virus

Adult female Swiss mice showed a greater resistance to intraperitoneal (i.p.) infection with encephalomyocarditis virus (EMCV) than male mice. This difference was not observed in weanling mice, in castrated adult mice or in adult mice injected intracerebrally. Administration of antibody to mouse interferon alpha/beta enhanced the virulence of EMCV for both sexes and no difference was then observed in susceptibility between male and female mice. Six h after EMCV infection, serum interferon titres were higher in adult female mice than in male mice. There was a close correlation between the early serum interferon titre (at 6 h) and survival of EMCV-infected mice. No differences in serum interferon titres were observed between male or female weanling mice or castrated adult mice. Potent preparations of exogenous interferon provided the same degree of protection against EMCV infection in male and female mice. We conclude that the more marked early interferon response of female mice to i.p. EMCV infection is one of the important factors underlying the differential susceptibility to EMCV. It is possible that the interferon system is also involved in the reported greater prevalence of picornavirus infections of men compared with women

Is nasal carriage of the main acquisition pathway for surgical-site infection in orthopaedic surgery?

International audienceThe endogenous or exogenous origin of , responsible for orthopaedic surgical-site infections (SSI), remains debated. We conducted a multicentre prospective cohort study to analyse the respective part of exogenous contamination and endogenous self-inoculation by during elective orthopaedic surgery. The nose of each consecutive patient was sampled before surgery. Strains of isolated from the nose and the wound, in the case of SSI, were compared by antibiotypes or pulsed-field gel electrophoresis (PFGE). A total of 3,908 consecutive patients undergoing orthopaedic surgery were included. Seventy-seven patients developed an SSI (2%), including 22 related to (0.6%). was isolated from the nose of 790 patients (20.2%) at the time of surgery. In the multivariate analysis, nasal carriage was found to be a risk factor for SSI in orthopaedic surgery. However, only nine subjects exhibiting SSI had been found to be carriers before surgery: when compared, three pairs of strains were considered to be different and six similar. In most cases of SSI, either an endogenous origin could not be demonstrated or pre-operative nasal colonisation retrieved a strain that was different from the one recovered from the surgical sit

Place des microbicides vaginaux dans la prévention de l'infection par le virus de l'immunodéficience humaine

Les microbicides peuvent se définir comme des substances topiques susceptibles de réduire le risque d'infections sexuellement transmissibles. L'objet de cette revue est de présenter un état des lieux des connaissances relatives aux microbicides vaginaux susceptibles de protéger les femmes contre l'infection par le virus de l'immunodéficience humaine de type 1 (VIH-1). Les molécules microbicides à visée anti-VIH comprennent des composés non spécifiques comme les détergents, les polyanions ou les inhibiteurs d'entrée, et des molécules spécifiques de VIH-1 qui incluent principalement des inhibiteurs des étapes précoces de l'infection virale et des inhibiteurs de la réverse transcriptase. Bien que l'approche microbicide soit très séduisante sous l'angle conceptuel, aucun essai clinique contrôlé et randomisé, conduit avec des molécules de première génération n'a fait la preuve de l'efficacité préventive de ces composés contre l'infection par VIH-1. Des résultats encourageants ont été obtenus chez des primates non humains et plusieurs essais cliniques menés à travers le monde devraient livrer leur verdict assez vite. Cette revue discute ces différents aspects et encore l'évaluation préclinique de la balance bénéfices-risques des produits microbicides, les associations de composés microbicides anti-VIH-1 et la capacité de ces substances à sélectionner des mutants résistants. Une meilleure connaissance des modes de franchissement de la muqueuse cervico-vaginale par VIH-1 devrait permettre d'affiner les stratégies microbicides qui, en l'absence de vaccination préventive à moyen terme, constituent une alternative à évaluer pour protéger les femmes — et notamment les plus vulnérables d'entre elles — vis-à-vis de l'infection par VIH-1

Screening a Peptide Library by DSC and SAXD: Comparison with the Biological Function of the Parent Proteins

We have recently identified the membranotropic regions of the hepatitis C virus proteins E1, E2, core and p7 proteins by observing the effect of protein-derived peptide libraries on model membrane integrity. We have studied in this work the ability of selected sequences of these proteins to modulate the Lβ-Lα and Lα-HII phospholipid phase transitions as well as check the viability of using both DSC and SAXD to screen a protein-derived peptide library. We demonstrate that it is feasible to screen a library of peptides corresponding to one or several proteins by both SAXD and DSC. This methodological combination should allow the identification of essential regions of membrane-interacting proteins which might be implicated in the molecular mechanism of membrane fusion and/or budding

Revisiting the B-cell compartment in mouse and humans: more than one B-cell subset exists in the marginal zone and beyond.

International audienceABSTRACT: The immunological roles of B-cells are being revealed as increasingly complex by functions that are largely beyond their commitment to differentiate into plasma cells and produce antibodies, the key molecular protagonists of innate immunity, and also by their compartmentalisation, a more recently acknowledged property of this immune cell category. For decades, B-cells have been recognised by their expression of an immunoglobulin that serves the function of an antigen receptor, which mediates intracellular signalling assisted by companion molecules. As such, B-cells were considered simple in their functioning compared to the other major type of immune cell, the T-lymphocytes, which comprise conventional T-lymphocyte subsets with seminal roles in homeostasis and pathology, and non-conventional T-lymphocyte subsets for which increasing knowledge is accumulating. Since the discovery that the B-cell family included two distinct categories - the non-conventional, or extrafollicular, B1 cells, that have mainly been characterised in the mouse; and the conventional, or lymph node type, B2 cells - plus the detailed description of the main B-cell regulator, FcγRIIb, and the function of CD40+ antigen presenting cells as committed/memory B-cells, progress in B-cell physiology has been slower than in other areas of immunology. Cellular and molecular tools have enabled the revival of innate immunity by allowing almost all aspects of cellular immunology to be re-visited. As such, B-cells were found to express "Pathogen Recognition Receptors" such as TLRs, and use them in concert with B-cell signalling during innate and adaptive immunity. An era of B-cell phenotypic and functional analysis thus began that encompassed the study of B-cell microanatomy principally in the lymph nodes, spleen and mucosae. The novel discovery of the differential localisation of B-cells with distinct phenotypes and functions revealed the compartmentalisation of B-cells. This review thus aims to describe novel findings regarding the B-cell compartments found in the mouse as a model organism, and in human physiology and pathology. It must be emphasised that some differences are noticeable between the mouse and human systems, thus increasing the complexity of B-cell compartmentalisation. Special attention will be given to the (lymph node and spleen) marginal zones, which represent major crossroads for B-cell types and functions and a challenge for understanding better the role of B-cell specificities in innate and adaptive immunology

Switching to dual/monotherapy determines an increase in CD8+ in HIV-infected individuals: An observational cohort study

Background: The CD4/CD8 ratio has been associated with the risk of AIDS and non-AIDS events. We describe trends in immunological parameters in people who underwent a switch to monotherapy or dual therapy, compared to a control group remaining on triple antiretroviral therapy (ART). Methods: We included patients in Icona who started a three-drug combination ART regimen from an ART-naïve status and achieved a viral load ≤ 50 copies/mL; they were subsequently switched to another triple or to a mono or double regimen. Standard linear regression at fixed points in time (12-24 months after the switch) and linear mixed model analysis with random intercepts and slopes were used to compare CD4 and CD8 counts and their ratio over time according to regimen types (triple vs. dual and vs. mono). Results: A total of 1241 patients were included; 1073 switched to triple regimens, 104 to dual (72 with 1 nucleoside reverse transcriptase inhibitor (NRTI), 32 NRTI-sparing), and 64 to monotherapy. At 12 months after the switch, for the multivariable linear regression the mean change in the log10 CD4/CD8 ratio for patients on dual therapy was -0.03 (95% confidence interval (CI) -0.05, -0.0002), and the mean change in CD8 count was +99 (95% CI +12.1, +186.3), taking those on triple therapy as reference. In contrast, there was no evidence for a difference in CD4 count change. When using all counts, there was evidence for a significant difference in the slope of the ratio and CD8 count between people who were switched to triple (points/year change ratio = +0.056, CD8 = -25.7) and those to dual regimen (ratio = -0.029, CD8 = +110.4). Conclusions: We found an increase in CD8 lymphocytes in people who were switched to dual regimens compared to those who were switched to triple. Patients on monotherapy did not show significant differences. The long-term implications of this difference should be ascertained

Pathogen reduction/inactivation of products for the treatment of bleeding disorders:what are the processes and what should we say to patients?

Patients with blood disorders (including leukaemia, platelet function disorders and coagulation factor deficiencies) or acute bleeding receive blood-derived products, such as red blood cells, platelet concentrates and plasma-derived products. Although the risk of pathogen contamination of blood products has fallen considerably over the past three decades, contamination is still a topic of concern. In order to counsel patients and obtain informed consent before transfusion, physicians are required to keep up to date with current knowledge on residual risk of pathogen transmission and methods of pathogen removal/inactivation. Here, we describe pathogens relevant to transfusion of blood products and discuss contemporary pathogen removal/inactivation procedures, as well as the potential risks associated with these products: the risk of contamination by infectious agents varies according to blood product/region, and there is a fine line between adequate inactivation and functional impairment of the product. The cost implications of implementing pathogen inactivation technology are also considered