title: Human TNF-α induces differential protein phosphorylation in Schistosoma mansoni adult male worms.
abstract: Schistosoma mansoni and its vertebrate host have a complex and intimate connection in which several molecular stimuli are exchanged and affect both organisms. Human tumor necrosis factor alpha (hTNF-α), a pro-inflammatory cytokine, is known to induce large-scale gene expression changes in the parasite and to affect several parasite biological processes such as metabolism, egg laying, and worm development. Until now, the molecular mechanisms for TNF-α activity in worms are not completely understood. Here, we aimed at exploring the effect of hTNF-α on S. mansoni protein phosphorylation by 2D gel electrophoresis followed by a quantitative analysis of phosphoprotein staining and protein identification by mass spectrometry. We analyzed three biological replicates of adult male worms exposed to hTNF-α and successfully identified 32 protein spots with a statistically significant increase in phosphorylation upon in vitro exposure to hTNF-α. Among the differentially phosphorylated proteins, we found proteins involved in metabolism, such as glycolysis, galactose metabolism, urea cycle, and aldehyde metabolism, as well as proteins related to muscle contraction and to cytoskeleton remodeling. The most differentially phosphorylated protein (30-fold increase in phosphorylation) was 14-3-3, whose function is known to be modulated by phosphorylation, belonging to a signal transduction protein family that regulates a variety of processes in all eukaryotic cells. Further, 75% of the identified proteins are known in mammals to be related to TNF-α signaling, thus suggesting that TNF-α response may be conserved in the parasite. We propose that this work opens new perspectives to be explored in the study of the molecular crosstalk between host and pathogen.
authors.affiliation: Núcleo de Enteroparasitas, Centro de Parasitologia e Micologia, Instituto Adolfo Lutz, 01614-000, São Paulo, SP, Brazil.|Disciplina de Parasitologia, Departamento de Microbiologia, Imunologia e Parasitologia, Universidade Federal de São Paulo, São Paulo, Brazil.
authors.forename: Katia C
authors.initials: KC
authors.lastname: Oliveira
authors.affiliation: Departamento de Bioquímica, Instituto de Química, Universidade de São Paulo, 05508-900, São Paulo, SP, Brazil.
authors.forename: Mariana L P
authors.initials: ML
authors.lastname: Carvalho
authors.affiliation: Departamento de Bioquímica, Instituto de Química, Universidade de São Paulo, 05508-900, São Paulo, SP, Brazil.
authors.forename: José Matheus C
authors.initials: JM
authors.lastname: Bonatto
authors.affiliation: Departamento de Bioquímica, Instituto de Química, Universidade de São Paulo, 05508-900, São Paulo, SP, Brazil.
authors.forename: Debora
authors.initials: D
authors.lastname: Schechtman
authors.affiliation: Departamento de Bioquímica, Instituto de Química, Universidade de São Paulo, 05508-900, São Paulo, SP, Brazil. verjo@iq.usp.br.|Instituto Butantan, 05503-900, São Paulo, SP, Brazil. verjo@iq.usp.br.
authors.forename: Sergio
authors.initials: S
authors.lastname: Verjovski-Almeida
mesh_terms: D000818:Animals; D004734:Energy Metabolism / Q000187:drug effects; D063990:Gene Ontology; D015801:Helminth Proteins / Q000235:genetics / Q000378:metabolism; D006790:Host-Parasite Interactions; D006801:Humans; D008297:Male; D013058:Mass Spectrometry; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D012550:Schistosoma mansoni / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
chemical_list: D015801:Helminth Proteins; D010750:Phosphoproteins; D014409:Tumor Necrosis Factor-alpha
keywords: Host-parasite interaction; Human TNF-α; Mass spectrometry; Phosphoproteomic analysis; Schistosoma mansoni; Signaling