ABSTRACT
The last step of Leishmania intracellular life cycle is the egress of amastigotes from the host cell and their uptake by adjacent cells. Using multidimensional live imaging of long-term-infected macrophage cultures we observed that Leishmania amazonensis amastigotes were transferred from cell to cell when the donor host macrophage delivers warning signs of imminent apoptosis. They were extruded from the macrophage within zeiotic structures (membrane blebs, an apoptotic feature) rich in phagolysosomal membrane components. The extrusions containing amastigotes were selectively internalized by vicinal macrophages and the rescued amastigotes remain viable in recipient macrophages. Host cell apoptosis induced by micro-irradiation of infected macrophage nuclei promoted amastigotes extrusion, which were rescued by non-irradiated vicinal macrophages. Using amastigotes isolated from LAMP1/LAMP2 knockout fibroblasts, we observed that the presence of these lysosomal components on amastigotes increases interleukin 10 production. Enclosed within host cell membranes, amastigotes can be transferred from cell to cell without full exposure to the extracellular milieu, what represents an important strategy developed by the parasite to evade host immune system.
Subject(s)
Leishmania/pathogenicity , Leishmaniasis/transmission , Lysosomal Membrane Proteins/metabolism , Lysosomal-Associated Membrane Protein 2/metabolism , Macrophages/parasitology , Animals , Apoptosis , Cell Line , Cell Membrane/parasitology , Fibroblasts , Interleukin-10/biosynthesis , Leishmaniasis/pathology , Lysosomal-Associated Membrane Protein 2/genetics , Lysosomal Membrane Proteins/genetics , Mice , Mice, Inbred BALB C , Mice, Inbred C57BLABSTRACT
COVID-19 vaccination during pregnancy is safe and effective in reducing the risk of complications. However, the uptake is still below targets worldwide. This study aimed to explore the factors associated with COVID-19 vaccination uptake among pregnant women since data on this topic is scarce in low-to-middle-income countries. A retrospective cohort study included linked data on COVID-19 vaccination and pregnant women who delivered a singleton live birth from August 1, 2021, to July 31, 2022, in Rio de Janeiro City, Brazil. Multiple logistic regression was performed to identify factors associated with vaccination during pregnancy, applying a hierarchical model and describing odds ratio with 95% confidence intervals. Of 65,304 pregnant women included in the study, 53.0% (95% CI, 52-53%) received at least one dose of COVID-19 vaccine during pregnancy. Higher uptake was observed among women aged older than 34 (aOR 1.21, 95%CI 1.15-1.28), black (aOR 1.10, 1.04-1.16), or parda/brown skin colour (aOR 1.05, 1.01-1.09), with less than eight years of education (aOR 1.09, 1.02-1.17), living without a partner (aOR 2.24, 2.16-2.34), more than six antenatal care appointments (aOR 1.92, 1.75-2.09), and having a previous child loss (OR 1.06, 1.02-1.11). These results highlight the need for targeted educational campaigns, trustful communication, and accessibility strategies for specific populations to improve vaccination uptake during pregnancy.