CD14<sup>+</sup>monocytes are the main leucocytic sources of CXCL10 in response to<i>Plasmodium falciparum</i>

Ioannidis, Lisa J; Eriksson, Emily M.; Hansen, Diana S.

doi:10.1017/s0031182019001744

Cited by 8 publications

(6 citation statements)

References 42 publications

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“…However, when the disease's circumstances become complicated and severe (as in CM), higher CXCL10 levels are detected in the blood circulation of patients [4][5][6] . Of note, although it appears that monocytes are one of the main sources of production of CXCL10 in response to P. falciparum infection 64 , this chemokine is released also by other cells such as neutrophils, eosinophils, and dendritic cells [65][66][67] . If and how the parasite communicates with these other host cells to alter CXCL10 production remains unknown.…”

Section: Discussionmentioning

confidence: 99%

Malaria parasites both repress host CXCL10 and use it as a cue for growth acceleration

et al. 2021

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Pathogens are thought to use host molecular cues to control when to initiate life-cycle transitions, but these signals are mostly unknown, particularly for the parasitic disease malaria caused by Plasmodium falciparum. The chemokine CXCL10 is present at high levels in fatal cases of cerebral malaria patients, but is reduced in patients who survive and do not have complications. Here we show a Pf ‘decision-sensing-system’ controlled by CXCL10 concentration. High CXCL10 expression prompts P. falciparum to initiate a survival strategy via growth acceleration. Remarkably, P. falciparum inhibits CXCL10 synthesis in monocytes by disrupting the association of host ribosomes with CXCL10 transcripts. The underlying inhibition cascade involves RNA cargo delivery into monocytes that triggers RIG-I, which leads to HUR1 binding to an AU-rich domain of the CXCL10 3’UTR. These data indicate that when the parasite can no longer keep CXCL10 at low levels, it can exploit the chemokine as a cue to shift tactics and escape.

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Section: Discussionmentioning

confidence: 99%

Malaria parasites both repress host CXCL10 and use it as a cue for growth acceleration

et al. 2021

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“…To further corroborate the pathological role of CXCL-10 in malaria, elevated levels of this molecule were associated with increased risk of fatal cerebral malaria in children [ 68 ]. In a recent study, CD14 + monocytes were identified as the main producers of CXCL-10 when challenged with P. falciparum , but the sub-sets that were involved and the association between CXCL-10 levels and parasite burden in humans remain unknown [ 69 ]. In addition, using an in vitro model of human blood monocyte-derived microglia cells, the uptake of IE-derived extracellular vesicles was shown to cause down-regulation of IL-6 and IL-10 gene expression [ 70 ].…”

Section: Heterogeneity In Host Phagocyte Subpopulations: Who Is the Big Eater?mentioning

confidence: 99%

Factors influencing phagocytosis of malaria parasites: the story so far

Chua

Yap

et al. 2021

Malar J

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There are seven known species of Plasmodium spp. that can infect humans. The human host can mount a complex network of immunological responses to fight infection and one of these immune functions is phagocytosis. Effective and timely phagocytosis of parasites, accompanied by the activation of a regulated inflammatory response, is beneficial for parasite clearance. Functional studies have identified specific opsonins, particularly antibodies and distinct phagocyte sub-populations that are associated with clinical protection against malaria. In addition, cellular and molecular studies have enhanced the understanding of the immunological pathways and outcomes following phagocytosis of malaria parasites. In this review, an integrated view of the factors that can affect phagocytosis of infected erythrocytes and parasite components, the immunological consequences and their association with clinical protection against Plasmodium spp. infection is provided. Several red blood cell disorders and co-infections, and drugs that can influence phagocytic capability during malaria are also discussed. It is hoped that an enhanced understanding of this immunological process can benefit the design of new therapeutics and vaccines to combat this infectious disease.

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“…IP-10 is also known to be a pro-tumorigenic chemokine that has been strongly correlated with the progression of breast cancer given that it is more largely secreted by the malignant than non-malignant tissues [ 14 ]. IP-10 is produced by multiple cell types, such as activated monocytes, macrophages, neutrophils, DCs, pre-adipocytes/adipocytes, hepatocytes, astrocytes, endothelial cells, keratinocytes, fibroblasts, mesenchymal cells, and pancreatic β cells [ 9 , 15 , 16 , 17 ] as well as by breast tumor cells, per se [ 18 ]. IP-10 expression is induced by lipopolysaccharide and proinflammatory cytokines, including IL-1 and tumor necrosis factor-α (TNFα) [ 19 , 20 ].…”

Section: Introductionmentioning

confidence: 99%

TNF-α Increases IP-10 Expression in MCF-7 Breast Cancer Cells via Activation of the JNK/c-Jun Pathways

et al. 2021

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IP-10 (also called CXCL10) plays a significant role in leukocyte homing to inflamed tissues, and increased IP-10 levels are associated with the pathologies of various inflammatory disorders, including type 2 diabetes, atherosclerosis, and cancer. TNF-α is a potent activator of immune cells and induces inflammatory cytokine expression in these cells. However, it is unclear whether TNF-α is able to induce IP-10 expression in MCF-7 breast cancer cells. We therefore determined IP-10 expression in TNF-α-treated MCF-7 cells and investigated the mechanism involved. Our data show that TNF-α induced/upregulated the IP-10 expression at both mRNA and protein levels in MCF-7 cells. Inhibition of JNK (SP600125) significantly suppressed the TNF-α-induced IP-10 in MCF-7 cells, while the inhibition of p38 MAPK (SB203580), MEK1/2 (U0126), and ERK1/2 (PD98059) had no significant effect. Furthermore, TNF-α-induced IP-10 expression was abolished in MCF-7 cells deficient in JNK. Similar results were obtained using MCF-7 cells deficient in c-Jun. Moreover, the JNK kinase inhibitor markedly reduced the TNF-α-induced JNK and c-Jun phosphorylation. The kinase activity of JNK induced by TNF-α stimulation of MCF-7 cells was significantly inhibited by SP600125. Altogether, our novel findings provide the evidence that TNF-α induces IP-10 expression in MCF-7 breast cancer cells via activation of the JNK/c-Jun signaling pathway.

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CD14⁺monocytes are the main leucocytic sources of CXCL10 in response toPlasmodium falciparum

Cited by 8 publications

References 42 publications

Malaria parasites both repress host CXCL10 and use it as a cue for growth acceleration

Malaria parasites both repress host CXCL10 and use it as a cue for growth acceleration

Factors influencing phagocytosis of malaria parasites: the story so far

TNF-α Increases IP-10 Expression in MCF-7 Breast Cancer Cells via Activation of the JNK/c-Jun Pathways

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CD14+monocytes are the main leucocytic sources of CXCL10 in response toPlasmodium falciparum

Cited by 8 publications

References 42 publications

Malaria parasites both repress host CXCL10 and use it as a cue for growth acceleration

Malaria parasites both repress host CXCL10 and use it as a cue for growth acceleration

Factors influencing phagocytosis of malaria parasites: the story so far

TNF-α Increases IP-10 Expression in MCF-7 Breast Cancer Cells via Activation of the JNK/c-Jun Pathways

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CD14⁺monocytes are the main leucocytic sources of CXCL10 in response toPlasmodium falciparum