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

Xi Zen Yap,James G Beeson,Joanne Pooley,Gaoqian Feng,Rachel J Lundie,Meredith O'Keeffe

doi:10.3389/fimmu.2019.00032

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.

Highlights

Dendritic cells (DCs) are key linkers of innate and adaptive immunity and their activation is essential to vaccination
CpG2216 was added to the cultures to ask whether the presence of pRBCs affected the activation of Flt3 ligand-induced DCs (FL-DCs) by an additional stimuli
MHCII and CD40 and CD86 co-stimulation molecule expression was measured upon FL-DCs (Figure 1)

Summary

Introduction

Dendritic cells (DCs) are key linkers of innate and adaptive immunity and their activation is essential to vaccination. Ablating DCs in murine models leads to vaccination failure and subsequent loss of antigen-specific T cells [1]. Immunization of individuals living in malaria-infested regions has been notoriously difficult, with even the most promising vaccines failing to provide high levels of efficacy. A failure to activate DCs in people infected with Plasmodium falciparum blood-stage parasites may provide some explanation to the low efficacy of malaria vaccines [reviewed in [2]]. It may explain the slow acquisition of natural anti-malarial immunity in individuals residing in malaria-endemic settings. The interaction between CD40 on DC and its ligand CD40L on T cells is integral to enhance both T cell and DC responses for effective adaptive immune responses [3]

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