7 research outputs found

    HIV-1 Promotes Intake of Leishmania Parasites by Enhancing Phosphatidylserine-Mediated, CD91/LRP-1-Dependent Phagocytosis in Human Macrophages

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    Over the past decade, the number of reported human immunodeficiency virus type-1 (HIV-1)/Leishmania co-infections has risen dramatically, particularly in regions where both diseases are endemic. Although it is known that HIV-1 infection leads to an increase in susceptibility to Leishmania infection and leishmaniasis relapse, little remains known on how HIV-1 contributes to Leishmania parasitaemia. Both pathogens infect human macrophages, and the intracellular growth of Leishmania is increased by HIV-1 in co-infected cultures. We now report that uninfected bystander cells, not macrophages productively infected with HIV-1, account for enhanced phagocytosis and higher multiplication of Leishmania parasites. This effect can be driven by HIV-1 Tat protein and transforming growth factor-beta (TGF-β). Furthermore, we show for the first time that HIV-1 infection increases surface expression of phosphatidylserine receptor CD91/LRP-1 on human macrophages, thereby leading to a Leishmania uptake by uninfected bystander cells in HIV-1-infected macrophage populations. The more important internalization of parasites is due to interactions between the scavenger receptor CD91/LRP-1 and phosphatidylserine residues exposed at the surface of Leishmania. We determined also that enhanced CD91/LRP-1 surface expression occurs rapidly following HIV-1 infection, and is triggered by the activation of extracellular TGF-β. Thus, these results establish an intricate link between HIV-1 infection, Tat, surface CD91/LRP-1, TGF-β, and enhanced Leishmania phosphatidylserine-mediated phagocytosis

    A call to caution when hydroxychloroquine is given to elderly COVID-19 patients.

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    INTRODUCTION: Hydroxychloroquine use in COVID-19 patients was widespread and uncontrolled until recently. Patients vulnerable to severe COVID-19 are at risk for hydroxychloroquine interactions with comorbidities and co-medications contributing to detrimental, including fatal adverse treatment effects. METHODS: This is a retrospective survey of health conditions and co-medications of COVID-19 patients who were pre-screened for enrolment into a randomized, double-blind, placebo-controlled hydroxychloroquine multicenter trial. RESULTS: Our survey involved 305 patients (median age 71 (IQR: 59-81) years). The majority of patients (N = 279, 92%) considered for inclusion into the clinical trial were not eligible mainly due to safety concerns caused by health conditions or co-medications. Most common were QT prolonging drugs (N = 188, 62%) and hematologic/hemato-oncologic diseases (N = 39, 13%) which prohibited the administration of hydroxychloroquine in our clinical trial. Additionally, 165 (54%) patients had health conditions and 167 (55%) were on co-medications that did not prohibit hydroxychloroquine treatment but had a risk of adverse interactions with hydroxychloroquine. Most common were diabetes (N = 86, 28%), renal insufficiency (N = 69, 23%) and heart failure (N = 58, 19%). CONCLUSION: The majority of hospitalized COVID-19 patients had health conditions or took co-medications precluding safe treatment with hydroxychloroquine. Therefore, especially in elderly, hydroxychloroquine should be administered with extreme caution and only in clinical trials
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