Human blood neutrophils generate ROS through FcγR-signaling to mediate protection against febrile P. falciparum malaria
Date
2023
Authors
Journal Title
Journal ISSN
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Publisher
Communications Biology
Abstract
Blood phagocytes, such as neutrophils and monocytes, generate reactive oxygen species
(ROS) as a part of host defense response against infections. We investigated the mechanism
of Fcγ-Receptor (FcγR) mediated ROS production in these cells to understand how they
contribute to anti-malarial immunity. Plasmodium falciparum merozoites opsonized with
naturally occurring IgG triggered both intracellular and extracellular ROS generation in blood
phagocytes, with neutrophils being the main contributors. Using specific inhibitors, we show
that both FcγRIIIB and FcγRIIA acted synergistically to induce ROS production in neutrophils,
and that NADPH oxidase 2 and the PI3K intracellular signal transduction pathway were
involved in this process. High levels of neutrophil ROS were also associated with protection
against febrile malaria in two geographically diverse malaria endemic regions from Ghana and
India, stressing the importance of the cooperation between anti-malarial IgG and neutrophils
in triggering ROS-mediated parasite killing as a mechanism for naturally acquired immunity
against malaria
Description
Research Article
Keywords
Blood phagocytes, malaria, Plasmodium falciparum