ORCID Profile
0000-0002-0895-3442
Current Organisations
University of Oxford
,
University of Oxford Saint Peter's College
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Publisher: Springer Science and Business Media LLC
Date: 17-12-2020
Publisher: American Society for Microbiology
Date: 12-2017
DOI: 10.1128/IAI.00191-17
Abstract: Epidemiological observations have linked increased host iron with malaria susceptibility, and perturbed iron handling has been hypothesized to contribute to the potentially life-threatening anemia that may accompany blood-stage malaria infection. To improve our understanding of these relationships, we examined the pathways involved in regulation of the master controller of iron metabolism, the hormone hepcidin, in malaria infection. We show that hepcidin upregulation in Plasmodium berghei murine malaria infection was accompanied by changes in expression of bone morphogenetic protein (BMP)/sons of mothers against decapentaplegic (SMAD) pathway target genes, a key pathway involved in hepcidin regulation. We therefore investigated known agonists of the BMP/SMAD pathway and found that Bmp gene expression was not increased in infection. In contrast, activin B, which can signal through the BMP/SMAD pathway and has been associated with increased hepcidin during inflammation, was upregulated in the livers of Plasmodium berghei -infected mice hepatic activin B was also upregulated at peak parasitemia during infection with Plasmodium chabaudi . Concentrations of the closely related protein activin A increased in parallel with hepcidin in serum from malaria-naive volunteers infected in controlled human malaria infection (CHMI) clinical trials. However, antibody-mediated neutralization of activin activity during murine malaria infection did not affect hepcidin expression, suggesting that these proteins do not stimulate hepcidin upregulation directly. In conclusion, we present evidence that the BMP/SMAD signaling pathway is perturbed in malaria infection but that activins, although raised in malaria infection, may not have a critical role in hepcidin upregulation in this setting.
Publisher: Elsevier BV
Date: 12-2022
Publisher: Frontiers Media SA
Date: 13-10-2016
Publisher: Springer Science and Business Media LLC
Date: 16-09-2015
DOI: 10.1038/SREP14081
Abstract: The assessment of naturally-acquired and vaccine-induced immunity to blood-stage Plasmodium falciparum malaria is of long-standing interest. However, the field has suffered from a paucity of in vitro assays that reproducibly measure the anti-parasitic activity induced by antibodies in conjunction with immune cells. Here we optimize the antibody-dependent respiratory burst (ADRB) assay, which assesses the ability of antibodies to activate the release of reactive oxygen species from human neutrophils in response to P. falciparum blood-stage parasites. We focus particularly on assay parameters affecting serum preparation and concentration and importantly assess reproducibility. Our standardized protocol involves testing each serum s le in singlicate with three independent neutrophil donors and indexing responses against a standard positive control of pooled hyper-immune Kenyan sera. The protocol can be used to quickly screen large cohorts of s les from in iduals enrolled in immuno-epidemiological studies or clinical vaccine trials and requires only 6 μL of serum per s le. Using a cohort of 86 s les, we show that malaria-exposed in iduals induce higher ADRB activity than malaria-naïve in iduals. The development of the ADRB assay complements the use of cell-independent assays in blood-stage malaria, such as the assay of growth inhibitory activity and provides an important standardized cell-based assay in the field.
Publisher: Elsevier BV
Date: 08-2020
Publisher: Elsevier BV
Date: 12-2020
Publisher: Elsevier BV
Date: 2021
Publisher: Public Library of Science (PLoS)
Date: 18-06-2013
Publisher: Oxford University Press (OUP)
Date: 21-10-2014
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for Susanne Hodgson.