Circulating neutrophil extracellular traps and neutrophil activation are increased in proportion to disease severity in human malaria

<p>Background: Neutrophil activation results in Plasmodium parasite killing in vitro, but neutrophil products including neutrophil extracellular traps (NETs) mediate host organ damage and may contribute to severe malaria. The role of NETs in the pathogenesis of severe malaria has not been exam...

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Príomhchruthaitheoirí: Kho, S, Minigo, G, Andries, B, Leonardo, L, Prayoga, P, Poespoprodjo, JR, Kenangalem, E, Price, RN, Woodberry, T, Anstey, NM, Yeo, TW
Formáid: Journal article
Teanga:English
Foilsithe / Cruthaithe: Oxford University Press 2018
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author Kho, S
Minigo, G
Andries, B
Leonardo, L
Prayoga, P
Poespoprodjo, JR
Kenangalem, E
Price, RN
Woodberry, T
Anstey, NM
Yeo, TW
author_facet Kho, S
Minigo, G
Andries, B
Leonardo, L
Prayoga, P
Poespoprodjo, JR
Kenangalem, E
Price, RN
Woodberry, T
Anstey, NM
Yeo, TW
author_sort Kho, S
collection OXFORD
description <p>Background: Neutrophil activation results in Plasmodium parasite killing in vitro, but neutrophil products including neutrophil extracellular traps (NETs) mediate host organ damage and may contribute to severe malaria. The role of NETs in the pathogenesis of severe malaria has not been examined.</p><p> Methods: In Papua, Indonesia, we enrolled adults with symptomatic Plasmodium falciparum (n = 47 uncomplicated, n = 8 severe), Plasmodium vivax (n = 37), or Plasmodium malariae (n = 14) malaria; asymptomatic P falciparum (n = 19) or P vivax (n = 21) parasitemia; and healthy adults (n = 23) without parasitemia. Neutrophil activation and NETs were quantified by immunoassays and microscopy and correlated with parasite biomass and disease severity.</p><p> Results: In patients with symptomatic malaria, neutrophil activation and NET counts were increased in all 3 Plasmodium species. In falciparum malaria, neutrophil activation and NET counts positively correlated with parasite biomass (Spearman rho = 0.41, P = .005 and r2 = 0.26, P = .002, respectively) and were significantly increased in severe disease. In contrast, NETs were inversely associated with parasitemia in adults with asymptomatic P falciparum infection (r2 = 0.24, P = .031) but not asymptomatic P vivax infection.</p><p> Conclusions: Although NETs may inhibit parasite growth in asymptomatic P falciparum infection, neutrophil activation and NET release may contribute to pathogenesis in severe falciparum malaria. Agents with potential to attenuate these processes should be evaluated.</p>
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spelling oxford-uuid:2f0003db-c2fd-482e-9ac6-f8cdf2ccdc052022-03-26T12:52:32ZCirculating neutrophil extracellular traps and neutrophil activation are increased in proportion to disease severity in human malariaJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:2f0003db-c2fd-482e-9ac6-f8cdf2ccdc05EnglishSymplectic Elements at OxfordOxford University Press2018Kho, SMinigo, GAndries, BLeonardo, LPrayoga, PPoespoprodjo, JRKenangalem, EPrice, RNWoodberry, TAnstey, NMYeo, TW<p>Background: Neutrophil activation results in Plasmodium parasite killing in vitro, but neutrophil products including neutrophil extracellular traps (NETs) mediate host organ damage and may contribute to severe malaria. The role of NETs in the pathogenesis of severe malaria has not been examined.</p><p> Methods: In Papua, Indonesia, we enrolled adults with symptomatic Plasmodium falciparum (n = 47 uncomplicated, n = 8 severe), Plasmodium vivax (n = 37), or Plasmodium malariae (n = 14) malaria; asymptomatic P falciparum (n = 19) or P vivax (n = 21) parasitemia; and healthy adults (n = 23) without parasitemia. Neutrophil activation and NETs were quantified by immunoassays and microscopy and correlated with parasite biomass and disease severity.</p><p> Results: In patients with symptomatic malaria, neutrophil activation and NET counts were increased in all 3 Plasmodium species. In falciparum malaria, neutrophil activation and NET counts positively correlated with parasite biomass (Spearman rho = 0.41, P = .005 and r2 = 0.26, P = .002, respectively) and were significantly increased in severe disease. In contrast, NETs were inversely associated with parasitemia in adults with asymptomatic P falciparum infection (r2 = 0.24, P = .031) but not asymptomatic P vivax infection.</p><p> Conclusions: Although NETs may inhibit parasite growth in asymptomatic P falciparum infection, neutrophil activation and NET release may contribute to pathogenesis in severe falciparum malaria. Agents with potential to attenuate these processes should be evaluated.</p>
spellingShingle Kho, S
Minigo, G
Andries, B
Leonardo, L
Prayoga, P
Poespoprodjo, JR
Kenangalem, E
Price, RN
Woodberry, T
Anstey, NM
Yeo, TW
Circulating neutrophil extracellular traps and neutrophil activation are increased in proportion to disease severity in human malaria
title Circulating neutrophil extracellular traps and neutrophil activation are increased in proportion to disease severity in human malaria
title_full Circulating neutrophil extracellular traps and neutrophil activation are increased in proportion to disease severity in human malaria
title_fullStr Circulating neutrophil extracellular traps and neutrophil activation are increased in proportion to disease severity in human malaria
title_full_unstemmed Circulating neutrophil extracellular traps and neutrophil activation are increased in proportion to disease severity in human malaria
title_short Circulating neutrophil extracellular traps and neutrophil activation are increased in proportion to disease severity in human malaria
title_sort circulating neutrophil extracellular traps and neutrophil activation are increased in proportion to disease severity in human malaria
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