Pregnancy Outcome and Placenta Pathology in Plasmodium berghei ANKA Infected Mice Reproduce the Pathogenesis of Severe Malaria in Pregnant Women

Pregnancy-associated malaria (PAM) is expressed in a range of clinical complications that include increased disease severity in pregnant women, decreased fetal viability, intra-uterine growth retardation, low birth weight and infant mortality. The physiopathology of malaria in pregnancy is difficult to scrutinize and attempts were made in the past to use animal models for pregnancy malaria studies. Here, we describe a comprehensive mouse experimental model that recapitulates many of the pathological and clinical features typical of human severe malaria in pregnancy. We used P. berghei ANKA-GFP infection during pregnancy to evoke a prominent inflammatory response in the placenta that entails CD11b mononuclear infiltration, up-regulation of MIP-1 alpha chemokine and is associated with marked reduction of placental vascular spaces. Placenta pathology was associated with decreased fetal viability, intra-uterine growth retardation, gross post-natal growth impairment and increased disease severity in pregnant females. Moreover, we provide evidence that CSA and HA, known to mediate P. falciparum adhesion to human placenta, are also involved in mouse placental malaria infection. We propose that reduction of maternal blood flow in the placenta is a key pathogenic factor in murine pregnancy malaria and we hypothesize that exacerbated innate inflammatory responses to Plasmodium infected red blood cells trigger severe placenta pathology. This experimental model provides an opportunity to identify cell and molecular components of severe PAM pathogenesis and to investigate the inflammatory response that leads to the observed fetal and placental blood circulation abnormalities

An African Muslim Saint and his Followers in France

This paper explores the practice of Islam among a relatively understudied group of Muslim migrants in France, the Halpulaaren, some of whom have been living in France for more than three decades. Drawing on field research in Senegal, Mali and France, the author considers the contexts for Halpulaaren migration to France, including the West African background to such migration and the situation migrants face in France. The author focuses on a Halpulaaren Muslim religious leader from Senegal, Mansour Baro, who has a reputation as a living Muslim saint, and his followers in France. Tierno Mansour is one of a handful of the most esteemed leaders of the Tijaniyya Sufi order in Senegal. The appeal of this saint, who annually visits Europe, for his followers in France is examined in order to try and understand some of the ways of being Muslim in the shadow of the global city with both its promises and constraints. [Journal abstract]ASC – Publicaties niet-programma gebonde

Oral abstracts of the 21st International AIDS Conference 18-22 July 2016, Durban, South Africa

The rate at which HIV-1 infected individuals progress to AIDS is highly variable and impacted by T cell immunity. CD8 T cell inhibitory molecules are up-regulated in HIV-1 infection and associate with immune dysfunction. We evaluated participants (n=122) recruited to the SPARTAC randomised clinical trial to determine whether CD8 T cell exhaustion markers PD-1, Lag-3 and Tim-3 were associated with immune activation and disease progression.Expression of PD-1, Tim-3, Lag-3 and CD38 on CD8 T cells from the closest pre-therapy time-point to seroconversion was measured by flow cytometry, and correlated with surrogate markers of HIV-1 disease (HIV-1 plasma viral load (pVL) and CD4 T cell count) and the trial endpoint (time to CD4 count <350 cells/μl or initiation of antiretroviral therapy). To explore the functional significance of these markers, co-expression of Eomes, T-bet and CD39 was assessed.Expression of PD-1 on CD8 and CD38 CD8 T cells correlated with pVL and CD4 count at baseline, and predicted time to the trial endpoint. Lag-3 expression was associated with pVL but not CD4 count. For all exhaustion markers, expression of CD38 on CD8 T cells increased the strength of associations. In Cox models, progression to the trial endpoint was most marked for PD-1/CD38 co-expressing cells, with evidence for a stronger effect within 12 weeks from confirmed diagnosis of PHI. The effect of PD-1 and Lag-3 expression on CD8 T cells retained statistical significance in Cox proportional hazards models including antiretroviral therapy and CD4 count, but not pVL as co-variants.Expression of ‘exhaustion’ or ‘immune checkpoint’ markers in early HIV-1 infection is associated with clinical progression and is impacted by immune activation and the duration of infection. New markers to identify exhausted T cells and novel interventions to reverse exhaustion may inform the development of novel immunotherapeutic approaches

Multiparental Population in Crops: Methods of Development and Dissection of Genetic Traits

International audienceMultiparental populations are located midway between association mapping that relies on germplasm collections and classic linkage analysis, based upon biparental populations. They provide several key advantages such as the possibility to include a higher number of alleles and increased level of recombination with respect to biparental populations, and more equilibrated allelic frequencies than association mapping panels. Moreover, in these populations new allele's combinations arise from recombination that may reveal transgressive phenotypes and make them a useful pre-breeding material. Here we describe the strategies for working with multiparental populations, focusing on nested association mapping populations (NAM) and multiparent advanced generation intercross populations (MAGIC). We provide details from the selection of founders, population development, and characterization to the statistical methods for genetic mapping and quantitative trait detection