Infected erythrocyte-derived extracellular vesicles alter vascular function via regulatory Ago2-miRNA complexes in malaria

Malaria remains one of the greatest public health challenges worldwide, particularly in sub-Saharan Africa. The clinical outcome of individuals infected with Plasmodium falciparum parasites depends on many factors including host systemic inflammatory responses, parasite sequestration in tissues and vascular dysfunction. Production of pro-inflammatory cytokines and chemokines promotes endothelial activation as well as recruitment and infiltration of inflammatory cells, which in turn triggers further endothelial cell activation and parasite sequestration. Inflammatory responses are triggered in part by bioactive parasite products such as hemozoin and infected red blood cell-derived extracellular vesicles (iRBC-derived EVs). Here we demonstrate that such EVs contain functional miRNA-Argonaute 2 complexes that are derived from the host RBC. Moreover, we show that EVs are efficiently internalized by endothelial cells, where the miRNA-Argonaute 2 complexes modulate target gene expression and barrier properties. Altogether, these findings provide a mechanistic link between EVs and vascular dysfunction during malaria infection

Sexual behaviors and their correlates among young people in Mauritius: a cross-sectional study

<p>Abstract</p> <p>Background</p> <p>Little is known about the HIV/AIDS epidemic in the Indian Ocean region, including Mauritius. National records suggest a prevalence of HIV in Mauritius of < 1% in the general population, which is one of the lowest prevalence rates in southern Africa. However, HIV-positive cases have been increasing recently in Mauritius. We conducted a cross-sectional survey in January 2003 to assess the prevalence of HIVrelated sexual behaviors and their correlates among young people aged 15–24 years in Mauritius.</p> <p>Methods</p> <p>We identified 1200 participants using two-stage cluster sampling. Demographic, social, sexual, and knowledge of HIV/AIDS data were obtained in face-to-face interviews using a structured questionnaire administered by trained interviewers. The prevalence of sexual behaviors was described in relation to gender, and the correlates of ever having had sex and nonuse of condom at last sex were analyzed using logistic regression.</p> <p>Results</p> <p>In the target population, 30.9% of males and 9.7% of females reported a history of sexual intercourse. Of the currently sexually active participants, 50.6% of men and 71.2% of women did not use condoms at their last sexual encounter. Logistic regression revealed that work experience and marijuana use were significantly associated with men's sexual experience, whereas being out of school and drinking experience were significantly associated with women's sexual experience. For both men and women, being Christian and visiting nightclubs were associated with having ever had sexual intercourse (P < 0.05). In addition, not using a condom at the first sexual encounter and lack of exposure to a nongovernmental organization (NGO) dealing with HIV/AIDS were associated with the nonuse of condoms at the last sexual encounter (P < 0.05).</p> <p>Conclusion</p> <p>Young people in Mauritius are at risk of a future HIV epidemic because behaviors predisposing to HIV infection are prevalent among sexually experienced youth. A focused prevention program targeting young people should be reinforced as part of the National AIDS Control Program, taking into account the predictors of sexual behaviors identified here.</p

Plasmodium falciparum Adhesion on Human Brain Microvascular Endothelial Cells Involves Transmigration-Like Cup Formation and Induces Opening of Intercellular Junctions

Cerebral malaria, a major cause of death during malaria infection, is characterised by the sequestration of infected red blood cells (IRBC) in brain microvessels. Most of the molecules implicated in the adhesion of IRBC on endothelial cells (EC) are already described; however, the structure of the IRBC/EC junction and the impact of this adhesion on the EC are poorly understood. We analysed this interaction using human brain microvascular EC monolayers co-cultured with IRBC. Our study demonstrates the transfer of material from the IRBC to the brain EC plasma membrane in a trogocytosis-like process, followed by a TNF-enhanced IRBC engulfing process. Upon IRBC/EC binding, parasite antigens are transferred to early endosomes in the EC, in a cytoskeleton-dependent process. This is associated with the opening of the intercellular junctions. The transfer of IRBC antigens can thus transform EC into a target for the immune response and contribute to the profound EC alterations, including peri-vascular oedema, associated with cerebral malaria