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Cited by 339Malaria Research and ControlHemoglobinopathies and Related DisordersErythrocyte Function and Pathophysiology

Early phagocytosis of glucose-6-phosphate dehydrogenase (G6PD)-deficient erythrocytes parasitized by Plasmodium falciparum may explain malaria protection in G6PD deficiency

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Cappadoro, Marina, Giribaldi, Giuliana, O'Brien, Estella, Turrini, Franco, Mannu, Franca, Ulliers, Daniela, Simula, Gino, Luzzatto, Lucio +1 more·1998·Blood
DOI 10.1182/blood.v92.7.2527
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Abstract

In population-based studies it has been established that inherited deficiency of erythrocyte (E) glucose-6-phosphate dehydrogenase (G6PD) confers protection against severe Plasmodium falciparum (P falciparum) malaria. Impaired growth of parasites in G6PD-deficient E in vitro has been reported in some studies, but not in others. In a systematic analysis, we have found that with five different strains of P falciparum (FCR-3, KI, C10, HB3B, and T9/96), there was no significant difference in either invasion or maturation when the parasites were grown in either normal or G6PD-deficient (Mediterranean variant) E. With all of these strains and at different maturation stages, we were unable to detect any difference in the amount of P falciparum-specific G6PD mRNA in normal versus deficient parasitized E. The rate of 14C-CO2 production from D-[1-14C] glucose (which closely reflects intracellular activity of G6PD) contributed by the parasite was very similar in intact normal and deficient E. By contrast, in studies of phagocytosis of parasitized E by human adherent monocytes, we found that when the parasites were at the ring stage (ring-stage parasitized E [RPE]), deficient RPE were phagocytosed 2.3 times more intensely than normal RPE (P = .001), whereas there was no difference when the parasites were at the more mature trophozoite stage (trophozoite-stage parasitized E [TPE]). Phagocytic removal markers (autologous IgG and complement C3 fragments) were significantly higher in deficient RPE than in normal RPE, while they were very similar in normal and deficient TPE. The level of reduced glutathione was remarkably lower in deficient RPE compared with normal RPE. We conclude that impaired antioxidant defense in deficient RPE may be responsible for membrane damage followed by phagocytosis. Because RPE, unlike TPE, are nontoxic to phagocytes, the increased removal by phagocytosis of RPE would reduce maturation to TPE and to schizonts and may be a highly efficient mechanism of malaria resistance in deficient subjects.

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  • Uptake of infected G6PD deficient red blood cells by myeloid cells appears to be enhanced, which downsizes the pathogen's habitat and undermines one of its key strategies of immune evasion.

    “Alternatively, the uptake of infected G6PD deficient RBC by myeloid cells appears to be enhanced which downsizes the pathogen's habitat and undermines one of its key strategies of immune evasion (Cappadoro et al., 1998).”

    From Iron in infection and immunity (2020) · cites this paper as Cappadoro et al., 1998

    The paper reports that human monocytes phagocytosed G6PD-deficient infected erythrocytes more intensely at the ring stage, and proposes that earlier removal limits parasitemia (phagocytosis results and discussion; page unavailable). It does not identify this effect as undermining a key immune-evasion strategy, and the enhanced uptake was not observed at the mature trophozoite stage. (LLM, conf=0.85)

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Research works printed but not linked: 2

  1. Luzzatto L, Sodeinde O, Martini G: Genetic variation in the host and adaptive phenomena in Plasmodium falciparum infection, in Malaria and the Red Cell. Ciba Foundation Symposium No 94. London, UK, Pitman, 1983, p 159
  2. Sambrook J, Fritsch EF, Maniatis T: Molecular cloning: A Laboratory Manual (ed 2). Cold Spring Harbor, NY, Cold Spring Harbor Laboratory Press, 1989

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Authors
Cappadoro, M., Giribaldi, G., O'Brien, E., Turrini, F., Mannu, F., Ulliers, D., Simula, G., Luzzatto, L., & Arese, P.
Affiliations
Hammersmith Hospital (GB)
ORCID
Venue
Blood
Publisher
American Society of Hematology
Published
1998-10-01
Volume
92
Issue
7
Pages
2527-2534
ISSN
  • 0006-4971 (ISSN-L)
  • 1528-0020
DOI
10.1182/blood.v92.7.2527
OpenAlex
W65176043
Cited by
339
References
44
Citations by year
2026: 4 · 2025: 1 · 2024: 3 · 2023: 9 · 2022: 7 · 2021: 10 · 2020: 14 · 2019: 9 · 2018: 12 · 2017: 8 · 2016: 10 · 2015: 42 · 2014: 27 · 2013: 16 · 2012: 14
FWCI
7.68
Type
journal article
Language
en
Open access
Locations
  • Blood (publishedVersion)
  • PubMed (publishedVersion)
  • Institutional Research Information System University of Turin (University of Turin) (submittedVersion)
Funders
  • World Health Organization
  • Compagnia di San Paolo
  • United Nations Development Programme
Topics
  • Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Malaria Research and Control
  • Health Sciences › Medicine › Genetics › Hemoglobinopathies and Related Disorders
  • Health Sciences › Medicine › Physiology › Erythrocyte Function and Pathophysiology
Keywords
glucose-6-phosphate dehydrogenase deficiency, Plasmodium falciparum, malaria resistance, phagocytosis, ring-stage parasites, monocytes, reduced glutathione, antioxidant defense, parasite maturation, complement C3, erythrocyte membrane damage
MeSH terms
Animals, Complement C3, Disease Susceptibility, Erythrocytes, Glucosephosphate Dehydrogenase, Glucosephosphate Dehydrogenase Deficiency, Glycolysis, Host-Parasite Interactions, Humans, Immunoglobulin G, Male, Monocytes, Opsonin Proteins, Phagocytosis, Plasmodium falciparum, RNA, Messenger, Malaria, Falciparum

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