急性 knowlesi 疟原虫和恶性疟原虫疟疾病人体内循环树突状细胞减少，尽管血浆 Flt3 配体水平升高。

Reduced circulating dendritic cells in acute Plasmodium knowlesi and Plasmodium falciparum malaria despite elevated plasma Flt3 ligand levels.

机构信息

Menzies School of Health Research and Charles Darwin University, Darwin, Australia.

QIMR Berghofer Medical Research Institute, Brisbane, Australia.

出版信息

Malar J. 2021 Feb 16;20(1):97. doi: 10.1186/s12936-021-03642-0.

DOI:10.1186/s12936-021-03642-0

PMID:33593383

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7888183/

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.

摘要

背景

恶性疟原虫（Plasmodium falciparum）感染会增加细胞因子 Fms 样酪氨酸激酶 3 配体（Flt3L）的血浆水平，Flt3L 是一种与树突状细胞（DC）扩增相关的造血因子。目前尚不清楚人畜共患寄生虫疟原虫 knowlesi 是否会影响人类疟疾中的 Flt3L 或 DC。本研究旨在探讨成人疟疾和亚临床实验感染中循环 DC 和 Flt3L 的相关性。

方法

在（i）志愿者中进行了 Plasmodium falciparum 实验感染，以及在马来西亚无并发症的（ii）P. falciparum 或（iii）P. knowlesi 疟疾患者中，评估了血浆 Flt3L 浓度以及血液 CD141 DC、CD1c DC 和浆细胞样 DC（pDC）的数量。

结果

恶性疟原虫感染导致疟疾成人患者所有循环 DC 亚群减少。急性 P. falciparum 和 P. knowlesi 疟疾患者的血浆 Flt3L 升高，而亚临床实验感染中没有增加。所有受检成人的循环 CD141 DC、CD1c DC 和 pDC 均下降，这是首次将急性疟疾中 DC 亚群下降的发现扩展到人畜共患寄生虫 P. knowlesi。

结论

在成人中，亚临床 Plasmodium 感染不会改变血浆 Flt3L，但会减少循环 DC。急性疟疾患者的血浆 Flt3L 浓度升高，但这一增加不足以恢复或扩增循环 CD141 DC、CD1c DC 或 pDC。这些数据表明，尚未确定的造血因子（而非 Flt3L）参与了循环 DC 的感知/维持，这些因子受到疟疾和亚临床感染的影响。人畜共患的 P. knowlesi 与其他疟原虫属在成人疟疾中使 DC 受损方面相似。