Inflammasome activation and IL-1 signaling during placental malaria induce poor pregnancy outcomes

Autor: Erika Paula Machado Peixoto, Vinícius Nunes Cordeiro Leal, Rosana Beatriz Duque Araujo, Carla Letícia Bandeira, Gerhard Wunderlich, Carlos Penha-Gonçalves, Rita Neres, Jamille Gregório Dombrowski, Claudio Romero Farias Marinho, Franciele Araujo, Vinícius M. Gomes, Aramys Silva Reis, Flávia Afonso Lima, André Barateiro, Sabrina Epiphanio, Fabio T. M. Costa, Giuseppe Palmisano, Lígia Antunes Gonçalves, Rodrigo Medeiros de Souza, Alessandra Pontillo, Karina R. Bortoluci, Leticia Labriola, Carsten Wrenger, Estela Bevilacqua, Oscar Murillo, Renato Barboza
Rok vydání: 2020
Předmět:
Inflammasomes
Plasmodium berghei
THP-1 Cells
Interleukin-1beta
BIOLOGIA CELULAR
Intrauterine growth restriction
Pathogenesis
Mice
0302 clinical medicine
Pregnancy
Immunopathology
Malaria
Falciparum
Research Articles
Mice
Knockout
0303 health sciences
Multidisciplinary
Caspase 1
SciAdv r-articles
Inflammasome
Trophoblasts
3. Good health
DNA-Binding Proteins
Female
Research Article
Signal Transduction
medicine.drug
musculoskeletal diseases
Immunology
Plasmodium falciparum
Cell Line
Interferon-gamma
03 medical and health sciences
AIM2
Immunity
parasitic diseases
NLR Family
Pyrin Domain-Containing 3 Protein
medicine
Animals
Humans
Immunologic Factors
030304 developmental biology
Innate immune system
Tumor Necrosis Factor-alpha
business.industry
Receptors
Interleukin-1
medicine.disease
Immunity
Innate
Malaria
Interleukin 1 Receptor Antagonist Protein
Gene Expression Regulation
Pregnancy Complications
Parasitic
business
030217 neurology & neurosurgery
Zdroj: Repositório Institucional da USP (Biblioteca Digital da Produção Intelectual)
Universidade de São Paulo (USP)
instacron:USP
Science Advances
ISSN: 2375-2548
DOI: 10.1126/sciadv.aax6346
Popis: IL-1 axis activation during placental malaria induces poor pregnancy outcomes that are obliterated after treatment with Anakinra.
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.
Databáze: OpenAIRE
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