Reduced circulating dendritic cells in acute Plasmodium knowlesi and Plasmodium falciparum malaria despite elevated plasma Flt3 ligand levels
Year: 2021
Type: article
Abstract: Background Plasmodium falciparummalaria increases plasma levels of the cytokine Fms-like tyrosine kinase 3 ligand (Flt3L), a haematopoietic factor associated with dendritic cell (DC) expansion. It is unknown if the zoonotic parasitePlasmodium knowlesiimpacts Flt3L or DC in human malaria. This study investigated circulating DC and Flt3L associations in adult malaria and in submicroscopic experimental infection. Methods Plasma Flt3L concentration and blood CD141+DC, CD1c+DC and plasmacytoid DC (pDC) numbers were assessed in (i) volunteers experimentally infected withP. falciparumand in Malaysian patients with uncomplicated (ii)P. falciparumor (iii)P. knowlesimalaria. Results Plasmodium knowlesicaused a decline in all circulating DC subsets in adults with malaria. Plasma Flt3L was elevated in acuteP. falciparumandP. knowlesimalaria with no increase in a subclinical experimental infection. Circulating CD141+DCs, CD1c+DCs and pDCs declined in all adults tested, for the first time extending the finding of DC subset decline in acute malaria to the zoonotic parasiteP. knowlesi. Conclusions In adults, submicroscopicPlasmodiuminfection causes no change in plasma Flt3L but does reduce circulating DCs. Plasma Flt3L concentrations increase in acute malaria, yet this increase is insufficient to restore or expand circulating CD141+DCs, CD1c+DCs or pDCs. These data imply that haematopoietic factors, yet to be identified and not Flt3L, involved in the sensing/maintenance of circulating DC are impacted by malaria and a submicroscopic infection. The zoonoticP. knowlesiis similar to otherPlasmodiumspp in compromising DC in adult malaria.
Source: Malaria Journal
Language: English
Topic: Malaria Research and Control
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,490
Awards: Dendritic cell dysfunction and apoptosis in malaria, Understanding the differences in immune responses during uncomplicated and severe falciparum and vivax malaria, Translational Studies in Malaria, T-follicular helper cell subtypes that induce protective anti-malaria antibodies, Comparative incidence and clinical spectrum of Plasmodium knowlesi malaria, a longitudinal study in Sabah, Malaysia, Understanding malaria in the human host, T-follicular helper cell subsets that induce protective anti-Plasmodium falciparum antibodies, Tropical diseases: Translating discoveries into better health, Risk factors, mechanisms, and treatment of knowlesi malaria, G7719967471, Discovering novel immune targets for treating infectious diseases, Tropical Disease - immunity, pathogenesis and vaccine development: global translation, Comparative pathophysiology of severe knowlesi and falciparum malaria, Pathophysiology and treatment of malaria and other tropical infectious diseases prevalent in our region
OpenAlex ID: W3130823574