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Tumor necrosis factor reduces Plasmodium falciparum growth and activates calcium signaling in human malaria parasites

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Cruz, Laura N., Wu, Yang, Ulrich, Henning, Craig, Alister ORCID: https://orcid.org/0000-0003-0914-6164 and Garcia, Célia R.S. (2016) 'Tumor necrosis factor reduces Plasmodium falciparum growth and activates calcium signaling in human malaria parasites'. Biochimica Et Biophysica Acta-General Subjects, Vol 1860, Issue 7, pp. 1489-1497.

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Abstract

Background:
Plasmodium has a complex biology including the ability to interact with host signals modulating their function through cellular machinery. Tumor necrosis factor (TNF) elicits diverse cellular responses including effects in malarial pathology and increased infected erythrocyte cytoadherence. As TNF levels are raised during P. falciparum infection we have investigated whether it has an effect on the parasite asexual stage.

Methods:
Flow cytometry, spectrofluorimetric determinations, confocal microscopy and PCR real time quantifications were employed for characterizing TNF induced effects and membrane integrity verified by wheat germ agglutinin staining.

Results:
TNF is able to decrease intracellular parasitemia, involving calcium as a second messenger of the pathway. Parasites incubated for 48h with TNF showed reduced erythrocyte invasion. Thus, TNF induced rises in intracellular calcium concentration, which were blocked by prior addition of the purinergic receptor agonists KN62 and A438079, or interfering with intra- or extracellular calcium release by thapsigargin or EGTA (ethylene glycol tetraacetic acid). Importantly, expression of PfPCNA1 which encodes the Plasmodium falciparum Proliferating-Cell Nuclear Antigen 1, decreased after P. falciparum treatment of TNF (tumor necrosis factor) or 6-Bnz cAMP (N6-Benzoyladenosine-3′,5′-cyclic monophosphate sodium salt).

Conclusions:
This is potentially interesting data showing the relevance of calcium in down regulating a gene involved in cellular proliferation, triggered by TNF.

General significance:
The data show that Plasmodium may subvert the immunological system and use TNF for the control of its proliferation within the vertebrate host.

Item Type: Article
Subjects: QU Biochemistry > Proteins. Amino Acids. Peptides > QU 55 Proteins
QW Microbiology and Immunology > Antigens and Antibodies. Toxins and Antitoxins > QW 630 Toxins. Antitoxins
QX Parasitology > Protozoa > QX 135 Plasmodia
WC Communicable Diseases > Tropical and Parasitic Diseases > WC 750 Malaria
Faculty: Department: Clinical Sciences & International Health > Clinical Sciences Department
Digital Object Identifer (DOI): https://doi.org/10.1016/j.bbagen.2016.04.003
Depositing User: Jessica Jones
Date Deposited: 18 Apr 2016 10:02
Last Modified: 17 Jul 2019 14:14
URI: https://archive.lstmed.ac.uk/id/eprint/5847

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