Dendritic Cells in
            <i>Plasmodium</i>
            Infection

Todryk, Stephen; Urban, Britta C.

doi:10.2217/17460913.3.3.279

Cited by 9 publications

(6 citation statements)

References 53 publications

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“…In addition, higher numbers of circulating BDCA-3 + mDCs have been detected in the blood of severely infected children combined with reduced immunostimulatory ability. This indicates that malaria may impair mDC functionality and suggests that the BDCA-3 + DC subset may play a crucial role in the immune response against the parasite in humans [16], [17].…”

Section: Introductionmentioning

confidence: 99%

Interethnic Differences in Antigen-Presenting Cell Activation and TLR Responses in Malian Children during Plasmodium falciparum Malaria

et al. 2011

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The Fulani ethnic group from West Africa is relatively better protected against Plasmodium falciparum malaria as compared to other sympatric ethnic groups, such as the Dogon. However, the mechanisms behind this lower susceptibility to malaria are largely unknown, particularly those concerning innate immunity. Antigen-presenting cells (APCs), and in particular dendritic cells (DCs) are important components of the innate and adaptive immune systems. Therefore, in this study we investigated whether APCs obtained from Fulani and Dogon children exhibited differences in terms of activation status and toll-like receptor (TLR) responses during malaria infection. Lower frequency and increased activation was observed in circulating plasmacytoid DCs and BDCA-3+ myeloid DCs of infected Fulani as compared to their uninfected counterparts. Conversely, a higher frequency and reduced activation was observed in the same DC subsets obtained from peripheral blood of P. falciparum-infected Dogon children as compared to their uninfected peers. Moreover, infected individuals of both ethnic groups exhibited higher percentages of both classical and inflammatory monocytes that were less activated as compared to their non-infected counterparts. In line with APC impairment during malaria infection, TLR4, TLR7 and TLR9 responses were strongly inhibited by P. falciparum infection in Dogon children, while no such TLR inhibition was observed in the Fulani children. Strikingly, the TLR-induced IFN-γ release was completely abolished in the Dogon undergoing infection while no difference was seen within infected and non-infected Fulani. Thus, P. falciparum infection is associated with altered activation status of important APC subsets and strongly inhibited TLR responses in peripheral blood of Dogon children. In contrast, P. falciparum induces DC activation and does not affect the innate response to specific TLR ligands in Fulani children. These findings suggest that DCs and TLR signalling may be of importance for the protective immunity against malaria observed in the Fulani.

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Section: Introductionmentioning

confidence: 99%

Interethnic Differences in Antigen-Presenting Cell Activation and TLR Responses in Malian Children during Plasmodium falciparum Malaria

et al. 2011

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“…The few studies directly investigating the impact of malaria on human DC function have yielded conflicting results. A recent balanced review attempts to resolves these apparent contradictions concluding that disparate findings could be explained by low‐dose immune induction vs. high‐dose immune suppression (89). The authors suggest the dose‐dependent DC response sequentially varies during the course of an individual infection from early, low‐dose responsiveness to late, high‐dose nonresponsiveness.…”

Section: A Pivotal Role For Innate Immunitymentioning

confidence: 99%

How might infant and paediatric immune responses influence malaria vaccine efficacy?

Moormann

2009

Parasite Immunology

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Naturally acquired immunity to malaria requires repeat infections yet does not engender sterile immunity or long-lasting protective immunologic memory. This renders infants and young children the most susceptible to malaria-induced morbidity and mortality, and the ultimate target for a malaria vaccine. The prevailing paradigm is that infants initially garner protection due to transplacentally transferred anti-malarial antibodies and other intrinsic factors such as foetal haemoglobin. As these wane infants have an insufficient immune repertoire to prevent genetically diverse Plasmodium infections and an inability to control malaria-induced immunopathology. This Review discusses humoral, cell-mediated and innate immune responses to malaria and how each contributes to protection – focusing on how deficiencies in infant and paediatric immune responses might influence malaria vaccine efficacy in this population. In addition, burgeoning evidence suggests a role for inhibitory receptors that limit immunopathology and guide the development of long-lived immunity. Precisely how age or malaria infections influence the function of these regulators is unknown. Therefore the possibility that infants may not have the immune-dexterity to balance effective parasite clearance with timely immune-regulation leading to protective immunologic memory is considered. And thus, malaria vaccines tested in adults and older children may not be predictive for trials conducted in infants.

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“…The activated DC and signals induced by cytokines together regulate Th1/Th2 development (9). In malaria, DC are the major early responders that produce pro-inflammatory cytokines, leading to NK and T cell activation and IFN-γ production (10)(11)(12). IFN-γ contributes to parasitemia control by priming phagocytes for clearance of parasites (13).…”

Section: Introductionmentioning

confidence: 99%

A malaria protein factor induces IL-4 production by dendritic cells via PI3K–Akt–NF-κB signaling independent of MyD88/TRIF and promotes Th2 response

Wu¹,

Gowda²,

Kawasawa

et al. 2018

Journal of Biological Chemistry

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Dendritic cells (DC) and cytokines produced by DC play crucial roles in inducing and regulating pro-/anti-inflammatory and Th1/Th2 responses. DC are known to produce Th1-promoting cytokine, IL-12, in response to malaria and other pathogenic infections, but it is thought that DC do not produce Th2-promoting cytokine, IL-4. Here, we show that a protein factor of malaria parasites induces IL-4 responses by CD11c hi MHCII hi CD3ε -

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Dendritic Cells in Plasmodium Infection

Cited by 9 publications

References 53 publications

Interethnic Differences in Antigen-Presenting Cell Activation and TLR Responses in Malian Children during Plasmodium falciparum Malaria

Interethnic Differences in Antigen-Presenting Cell Activation and TLR Responses in Malian Children during Plasmodium falciparum Malaria

How might infant and paediatric immune responses influence malaria vaccine efficacy?

A malaria protein factor induces IL-4 production by dendritic cells via PI3K–Akt–NF-κB signaling independent of MyD88/TRIF and promotes Th2 response

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