Dataset Information

Different Life Cycle Stages of Plasmodium falciparum Induce Contrasting Responses in Dendritic Cells.

ABSTRACT: Dendritic cells are key linkers of innate and adaptive immunity. Efficient dendritic cell activation is central to the acquisition of immunity and the efficacy of vaccines. Understanding how dendritic cells are affected by Plasmodium falciparum blood-stage parasites will help to understand how immunity is acquired and maintained, and how vaccine responses may be impacted by malaria infection or exposure. This study investigates the response of dendritic cells to two different life stages of the malaria parasite, parasitized red blood cells and merozoites, using a murine model. We demonstrate that the dendritic cell responses to merozoites are robust whereas dendritic cell activation, particularly CD40 and pro-inflammatory cytokine expression, is compromised in the presence of freshly isolated parasitized red blood cells. The mechanism of dendritic cell suppression by parasitized red blood cells is host red cell membrane-independent. Furthermore, we show that cryopreserved parasitized red blood cells have a substantially reduced capacity for dendritic cell activation.

SUBMITTER: Yap XZ

PROVIDER: S-EPMC6365426 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Different Life Cycle Stages of <i>Plasmodium falciparum</i> Induce Contrasting Responses in Dendritic Cells.

Yap Xi Zen XZ Lundie Rachel J RJ Feng Gaoqian G Pooley Joanne J Beeson James G JG O'Keeffe Meredith M

Frontiers in immunology 20190131

Dendritic cells are key linkers of innate and adaptive immunity. Efficient dendritic cell activation is central to the acquisition of immunity and the efficacy of vaccines. Understanding how dendritic cells are affected by <i>Plasmodium falciparum</i> blood-stage parasites will help to understand how immunity is acquired and maintained, and how vaccine responses may be impacted by malaria infection or exposure. This study investigates the response of dendritic cells to two different life stages ...[more]

PMID: 30766530

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Project description:BackgroundPlasmodium falciparum causes the majority of malaria cases worldwide and children in sub-Saharan Africa are the most vulnerable group affected. Non-sterile clinical immunity that protects from symptoms develops slowly and is relatively short-lived. Moreover, current malaria vaccine candidates fail to induce durable high-level protection in endemic settings, possibly due to the immunomodulatory effects of the malaria parasite itself. Because dendritic cells play a crucial role in initiating immune responses, the aim of this study was to better understand the impact of cumulative malaria exposure as well as concurrent P. falciparum infection on dendritic cell phenotype and function.MethodsIn this cross-sectional study, the phenotype and function of dendritic cells freshly isolated from peripheral blood samples of Malian adults with a lifelong history of malaria exposure who were either uninfected (n = 27) or asymptomatically infected with P. falciparum (n = 8) was assessed. Additionally, plasma cytokine and chemokine levels were measured in these adults and in Malian children (n = 19) with acute symptomatic malaria.ResultsWith the exception of lower plasmacytoid dendritic cell frequencies in asymptomatically infected Malian adults, peripheral blood dendritic cell subset frequencies and HLA-DR surface expression did not differ by infection status. Peripheral blood myeloid dendritic cells of uninfected Malian adults responded to in vitro stimulation with P. falciparum blood-stage parasites by up-regulating the costimulatory molecules HLA-DR, CD80, CD86 and CD40 and secreting IL-10, CXCL9 and CXCL10. In contrast, myeloid dendritic cells of asymptomatically infected Malian adults exhibited no significant responses above the uninfected red blood cell control. IL-10 and CXCL9 plasma levels were elevated in both asymptomatic adults and children with acute malaria.ConclusionsThe findings of this study indicate that myeloid dendritic cells of uninfected adults with a lifelong history of malaria exposure are able to up-regulate co-stimulatory molecules and produce cytokines. Whether mDCs of malaria-exposed individuals are efficient antigen-presenting cells capable of mounting an appropriate immune response remains to be determined. The data also highlights IL-10 and CXCL9 as important factors in both asymptomatic and acute malaria and add to the understanding of asymptomatic P. falciparum infections in malaria-endemic areas.

Dataset Information

Different Life Cycle Stages of Plasmodium falciparum Induce Contrasting Responses in Dendritic Cells.

Publications

Different Life Cycle Stages of <i>Plasmodium falciparum</i> Induce Contrasting Responses in Dendritic Cells.

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