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

Autor(es)

Cruz, Laura N. ^[1] ; Wu, Yang ^[2] ; Ulrich, Henning ^[3] ; Craig, Alister G. ^[2] ; Garcia, Celia R. S. ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Inst Biociencias, Dept Physiol, Rua Matao, Travessa 14, 321, BR-05508900 Sao Paulo, SP - Brazil

^[2] Univ Liverpool, Liverpool Sch Trop Med, Dept Parasitol, Liverpool L3 5QA, Merseyside - England

^[3] Univ Sao Paulo, Inst Quim, Dept Biochem, Sao Paulo, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS; v. 1860, n. 7, p. 1489-1497, JUL 2016.
• Citações Web of Science: 9

Resumo

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 Plasmodium 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 48 h 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 (N-6-benzoyladenosine-3',5'-cyclic monophosphate sodium salt). Conclusions: This is potentially interesting data showing the relevance of calcium in downregulating 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. (C) 2016 The Authors. Published by Elsevier B.V. (AU)

• Processo FAPESP: 11/51295-5 - Genômica funcional em Plasmodium
• Beneficiário: Célia Regina da Silva Garcia
• Modalidade de apoio: Auxílio à Pesquisa - Temático