Human blood neutrophils generate ROS through Fc gamma R-signaling to mediate protection against febrile P. falciparum malaria

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 Fc gamma-Receptor (Fc gamma R) 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 Fc gamma RIIIB and Fc gamma RIIA 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.

Automated summary

Blood phagocytes generate reactive oxygen species (ROS) in response to infections. The study investigates how Fc gamma receptors induce ROS production in neutrophils, contributing to anti-malarial immunity. Both Fc gamma RIIIB and Fc gamma RIIA synergistically induce ROS production in neutrophils, involving NADPH oxidase 2 and the PI3K pathway. The high levels of neutrophil ROS are associated with protection against febrile malaria, highlighting the importance of the cooperation between anti-malarial IgG and neutrophils.