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Study of signal transduction pathways in Schistosoma mansoni and their relevance in the host-pathogen interaction (SchistoSig)


Schistosomiasis is a serious problem of public health in Brazil and in the developing countries. It is caused by Schistosoma mansoni, a parasite that has a complex life cycle involving an intermediate (mollusk) and a definitive (human) host. The interaction between the parasite and its hosts has been a constant subject of study, highlighting the signaling elements as key factors for understanding the host-parasite interaction. In this context, the effect of human TNF-α on parasite's development and physiology has already been described. The description of the TNF-α receptor homologous gene in S. mansoni (SmTNFR) and the identification and characterization of homologous genes for the possible downstream signaling pathway has been the investigation subject of the proposing researcher throughout her training. The present proposal aims at studying the effect of human TNF-α on the parasite, observing its effect on the transcriptome, the mitotic activity rate and the morphology of the worms. The effect of human TNF-α on the parasite suggests its interaction with SmTNFR; nevertheless, we do not discard the possible existence of a parasite's own ligand. Thus, we intend to identify a potential endogenous ligand and to continue the study of TNF signaling in the parasite through the characterization of TRAF proteins (TNF Receptor Associated Factors) and their interactions with other signaling proteins. Finally we will evaluate the immunogenicity of the receptor in the definitive hosts (in the será of infected hamsters and patients) to verify its potential as an antigen for serological diagnosis of schistosomiasis. (AU)

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Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
BERTEVELLO, CLAUDIO R.; RUSSO, BRUNO R. A.; TAHIRA, ANA C.; LOPES-JUNIOR, EDNILSON HILARIO; DEMARCO, RICARDO; OLIVEIRA, KATIA C.. The evolution of TNF signaling in platyhelminths suggests the cooptation of TNF receptor in the host-parasite interplay. PARASITES & VECTORS, v. 13, n. 1, . (12/50115-6)
OLIVEIRA, KATIA C.; CARDOSO, RITA; DOS SANTOS, ANTONIO C.; FERNANDES, RUBEN; BOTELHO, MONICA C.. Imbalance of Steroid Hormones in Hamsters Infected with Schistosoma mansoni. ENDOCRINE METABOLIC & IMMUNE DISORDERS-DRUG TARGETS, v. 19, n. 8, p. 1122-1126, . (12/50115-6)
LOPES-JUNIOR, EDNILSON HILARIO; BERTEVELLO, CLAUDIO ROMERO; DE OLIVEIRA SILVEIRA, GILBERT; GUEDES, CAMILA BANCA; RODRIGUES, GRATCHELA DUTRA; RIBEIRO, VIVIANE SOUSA; AMARAL, MURILO SENA; KANAMURA, CRISTINA TAKAMI; PINTO, PEDRO LUIZ SILVA; KRUGER, RODRIGO FERREIRA; et al. Human tumor necrosis factor alpha affects the egg-laying dynamics and glucose metabolism of Schistosoma mansoni adult worms in vitro. PARASITES & VECTORS, v. 15, n. 1, p. 9-pg., . (12/50115-6)

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