Inflammasome Activation and IL-1 Signaling During Placental Malaria Induce Poor Pregnancy Outcomes

Overview

Journal Sci Adv

Specialties Biology
Science

Date 2020 Mar 18

PMID 32181339

Citations 30

Authors

Aramys S Reis

Renato Barboza

Oscar Murillo

Andre Barateiro

Erika P M Peixoto

Flavia A Lima

Vinicius M Gomes

Jamille G Dombrowski

Vinicius N C Leal

Franciele Araujo

Carla L Bandeira

Rosana B D Araujo

Rita Neres

Rodrigo M Souza

Fabio T M Costa

Alessandra Pontillo

Estela Bevilacqua

Carsten Wrenger

Gerhard Wunderlich

Giuseppe Palmisano

Leticia Labriola

Karina R Bortoluci

Carlos Penha-Goncalves

Ligia A Goncalves

Sabrina Epiphanio

Claudio R F Marinho

Affiliations

Soon will be listed here.

Abstract

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.

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