Science advances · 2020
Inflammasome activation and IL-1 signaling during placental malaria induce poor pregnancy outcomes.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод пока не подготовлен
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Reis Aramys S, Barboza Renato, Murillo Oscar, Barateiro André, Peixoto Erika P M, Lima Flávia A, Gomes Vinícius M, Dombrowski Jamille G, Leal Vinícius N C, Araujo Franciele, Bandeira Carla L, Araujo Rosana B D, Neres Rita, Souza Rodrigo M, Costa Fabio T M, Pontillo Alessandra, Bevilacqua Estela, Wrenger Carsten, Wunderlich Gerhard, Palmisano Giuseppe, Labriola Leticia, Bortoluci Karina R, Penha-Gonçalves Carlos, Gonçalves Lígia A, Epiphanio Sabrina, Marinho Claudio R F
Аннотация
Placental malaria (PM) is associated with severe inflammation leading to abortion, preterm delivery, and intrauterine growth restriction. Innate immunity responses play critical roles, but the mechanisms underlying placental immunopathology are still unclear. Here, we investigated the role of inflammasome activation in PM by scrutinizing human placenta samples from an endemic area and ablating inflammasome components in a PM mouse model. The reduction in birth weight in babies from infected mothers is paralleled by increased placental expression of AIM2 and NLRP3 inflammasomes. Using genetic dissection, we reveal that inflammasome activation pathways are involved in the production and detrimental action of interleukin-1β (IL-1β) in the infected placenta. The IL-1R pharmacological antagonist Anakinra improved pregnancy outcomes by restoring fetal growth and reducing resorption in an experimental model. These findings unveil that IL-1β-mediated signaling is a determinant of PM pathogenesis, suggesting that IL-1R antagonists can improve clinical outcomes of malaria infection in pregnancy.
Предметные рубрики MeSH
AnimalsCaspase 1Cell LineDNA-Binding ProteinsFemaleGene Expression RegulationHumansImmunity, InnateImmunologic FactorsInflammasomesInterferon-gammaInterleukin 1 Receptor Antagonist ProteinInterleukin-1betaMalariaMalaria, FalciparumMiceMice, KnockoutNLR Family, Pyrin Domain-Containing 3 ProteinPlasmodium bergheiPlasmodium falciparumPregnancyPregnancy Complications, ParasiticReceptors, Interleukin-1Signal TransductionTHP-1 CellsTrophoblastsTumor Necrosis Factor-alpha