Human blood neutrophils generate ROS through FcγR-signaling to mediate protection against febrile P. falciparum malaria
Research output: Contribution to journal › Journal article › Research › peer-review
Standard
Human blood neutrophils generate ROS through FcγR-signaling to mediate protection against febrile P. falciparum malaria. / Ofori, Ebenezer Addo; Garcia-Senosiain, Asier; Naghizadeh, Mohammad; Kana, Ikhlaq Hussain; Dziegiel, Morten Hanefeld; Adu, Bright; Singh, Subhash; Theisen, Michael.
In: Communications Biology , Vol. 6, 743, 2023.Research output: Contribution to journal › Journal article › Research › peer-review
Harvard
APA
Vancouver
Author
Bibtex
}
RIS
TY - JOUR
T1 - Human blood neutrophils generate ROS through FcγR-signaling to mediate protection against febrile P. falciparum malaria
AU - Ofori, Ebenezer Addo
AU - Garcia-Senosiain, Asier
AU - Naghizadeh, Mohammad
AU - Kana, Ikhlaq Hussain
AU - Dziegiel, Morten Hanefeld
AU - Adu, Bright
AU - Singh, Subhash
AU - Theisen, Michael
N1 - © 2023. The Author(s).
PY - 2023
Y1 - 2023
N2 - 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.
AB - 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.
U2 - 10.1038/s42003-023-05118-0
DO - 10.1038/s42003-023-05118-0
M3 - Journal article
C2 - 37463969
VL - 6
JO - Communications Biology
JF - Communications Biology
SN - 2399-3642
M1 - 743
ER -
ID: 359728159