Dendritic cell responses to Plasmodium falciparum in a malaria-endemic setting

• Published in: Malaria Journal
• Main Authors: Triniti C. Turner, Charles Arama, Aissata Ongoiba, Safiatou Doumbo, Didier Doumtabé, Kassoum Kayentao, Jeff Skinner, Shanping Li, Boubacar Traore, Peter D. Crompton, Anton Götz
• Format: Article in Journal/Newspaper
• Language: English
• Published: BMC 2021
• Subjects: Dendritic cells; Malaria; Plasmodium falciparum; Cytokines; Chemokines; Costimulatory molecules; Arctic medicine. Tropical medicine; RC955-962; Infectious and parasitic diseases; RC109-216; Arctic
• Online Access: https://doi.org/10.1186/s12936-020-03533-w; https://doaj.org/article/f4c72f0bae1242f1a9377a1569d3d7d4

Abstract Background Plasmodium 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. Methods In 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. Results With 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. Conclusions The findings of this study indicate that myeloid dendritic cells of uninfected adults with a lifelong history of malaria ...