Reduced circulating dendritic cells in acute Plasmodium knowlesi and Plasmodium falciparum malaria despite elevated plasma Flt3 ligand levels
Abstract Background Plasmodium falciparum malaria 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 parasite Plasmodium knowlesi impacts Flt3L or DC in human malaria....
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ftdoajarticles:oai:doaj.org/article:ceb09602cd7c423e8c2a5de4a5614c22 2023-05-15T15:12:50+02:00 Reduced circulating dendritic cells in acute Plasmodium knowlesi and Plasmodium falciparum malaria despite elevated plasma Flt3 ligand levels Jessica R. Loughland Tonia Woodberry Damian Oyong Kim A. Piera Fiona H. Amante Bridget E. Barber Matthew J. Grigg Timothy William Christian R. Engwerda Nicholas M. Anstey James S. McCarthy Michelle J. Boyle Gabriela Minigo 2021-02-01T00:00:00Z https://doi.org/10.1186/s12936-021-03642-0 https://doaj.org/article/ceb09602cd7c423e8c2a5de4a5614c22 EN eng BMC https://doi.org/10.1186/s12936-021-03642-0 https://doaj.org/toc/1475-2875 doi:10.1186/s12936-021-03642-0 1475-2875 https://doaj.org/article/ceb09602cd7c423e8c2a5de4a5614c22 Malaria Journal, Vol 20, Iss 1, Pp 1-8 (2021) IBSM Plasmodium falciparum Plasmodium knowlesi Dendritic cells CD141 BDCA3 Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 article 2021 ftdoajarticles https://doi.org/10.1186/s12936-021-03642-0 2022-12-31T06:12:03Z Abstract Background Plasmodium falciparum malaria 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 parasite Plasmodium knowlesi impacts 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 with P. falciparum and in Malaysian patients with uncomplicated (ii) P. falciparum or (iii) P. knowlesi malaria. Results Plasmodium knowlesi caused a decline in all circulating DC subsets in adults with malaria. Plasma Flt3L was elevated in acute P. falciparum and P. knowlesi malaria 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 parasite P. knowlesi. Conclusions In adults, submicroscopic Plasmodium infection 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 zoonotic P. knowlesi is similar to other Plasmodium spp in compromising DC in adult malaria. Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic Malaria Journal 20 1 |
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Directory of Open Access Journals: DOAJ Articles |
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IBSM Plasmodium falciparum Plasmodium knowlesi Dendritic cells CD141 BDCA3 Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 |
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IBSM Plasmodium falciparum Plasmodium knowlesi Dendritic cells CD141 BDCA3 Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 Jessica R. Loughland Tonia Woodberry Damian Oyong Kim A. Piera Fiona H. Amante Bridget E. Barber Matthew J. Grigg Timothy William Christian R. Engwerda Nicholas M. Anstey James S. McCarthy Michelle J. Boyle Gabriela Minigo Reduced circulating dendritic cells in acute Plasmodium knowlesi and Plasmodium falciparum malaria despite elevated plasma Flt3 ligand levels |
topic_facet |
IBSM Plasmodium falciparum Plasmodium knowlesi Dendritic cells CD141 BDCA3 Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 |
description |
Abstract Background Plasmodium falciparum malaria 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 parasite Plasmodium knowlesi impacts 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 with P. falciparum and in Malaysian patients with uncomplicated (ii) P. falciparum or (iii) P. knowlesi malaria. Results Plasmodium knowlesi caused a decline in all circulating DC subsets in adults with malaria. Plasma Flt3L was elevated in acute P. falciparum and P. knowlesi malaria 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 parasite P. knowlesi. Conclusions In adults, submicroscopic Plasmodium infection 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 zoonotic P. knowlesi is similar to other Plasmodium spp in compromising DC in adult malaria. |
format |
Article in Journal/Newspaper |
author |
Jessica R. Loughland Tonia Woodberry Damian Oyong Kim A. Piera Fiona H. Amante Bridget E. Barber Matthew J. Grigg Timothy William Christian R. Engwerda Nicholas M. Anstey James S. McCarthy Michelle J. Boyle Gabriela Minigo |
author_facet |
Jessica R. Loughland Tonia Woodberry Damian Oyong Kim A. Piera Fiona H. Amante Bridget E. Barber Matthew J. Grigg Timothy William Christian R. Engwerda Nicholas M. Anstey James S. McCarthy Michelle J. Boyle Gabriela Minigo |
author_sort |
Jessica R. Loughland |
title |
Reduced circulating dendritic cells in acute Plasmodium knowlesi and Plasmodium falciparum malaria despite elevated plasma Flt3 ligand levels |
title_short |
Reduced circulating dendritic cells in acute Plasmodium knowlesi and Plasmodium falciparum malaria despite elevated plasma Flt3 ligand levels |
title_full |
Reduced circulating dendritic cells in acute Plasmodium knowlesi and Plasmodium falciparum malaria despite elevated plasma Flt3 ligand levels |
title_fullStr |
Reduced circulating dendritic cells in acute Plasmodium knowlesi and Plasmodium falciparum malaria despite elevated plasma Flt3 ligand levels |
title_full_unstemmed |
Reduced circulating dendritic cells in acute Plasmodium knowlesi and Plasmodium falciparum malaria despite elevated plasma Flt3 ligand levels |
title_sort |
reduced circulating dendritic cells in acute plasmodium knowlesi and plasmodium falciparum malaria despite elevated plasma flt3 ligand levels |
publisher |
BMC |
publishDate |
2021 |
url |
https://doi.org/10.1186/s12936-021-03642-0 https://doaj.org/article/ceb09602cd7c423e8c2a5de4a5614c22 |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
Malaria Journal, Vol 20, Iss 1, Pp 1-8 (2021) |
op_relation |
https://doi.org/10.1186/s12936-021-03642-0 https://doaj.org/toc/1475-2875 doi:10.1186/s12936-021-03642-0 1475-2875 https://doaj.org/article/ceb09602cd7c423e8c2a5de4a5614c22 |
op_doi |
https://doi.org/10.1186/s12936-021-03642-0 |
container_title |
Malaria Journal |
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20 |
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1 |
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1766343472709632000 |