Human tumor necrosis factor alpha affects the egg-laying dynamics and glucose metabolism of Schistosoma mansoni adult worms in vitro

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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 ; Verjovski-Almeida, Sergio ; Oliveira, Katia Cristina

• Document type: Journal article
• Source: PARASITES & VECTORS; v. 15, n. 1, p. 9-pg., 2022-05-24.

Abstract

Several studies have described the effects of human tumor necrosis factor alpha (hTNF-alpha) on Schistosoma mansoni. hTNF-alpha affects the worm's development, metabolism, egg-laying, gene expression and protein phosphorylation. The available data on the influence of hTNF-alpha on egg-laying in S. mansoni are controversial, but understanding the mechanism of egg-laying regulation in this species is essential in combating schistosomiasis. We characterized the effects of in vitro treatment of S. mansoni adult worms with different doses of hTNF-alpha (5, 20 and 40 ng/ml) for 5 days. We explored the effects on egg-laying rate, glucose levels, ATP metabolism, and messenger RNA (mRNA) expression levels of lactate dehydrogenase, glucose transporters and the parasite gene which acts as an hTNF-alpha receptor, SmTNFR. hTNF-alpha influenced egg-laying in a time- and dose-dependent manner: at a dose of 40 ng/ml, egg-laying increased on day 2 and decreased on days 3 and 4; at 20 ng/ml, egg-laying decreased on day 3; while at 5 ng/ml, egg-laying decreased on day 4. The total number of eggs produced was not affected by the different treatments, but the egg-laying dynamics were: the median egg-laying time decreased significantly with treatment, and egg developmental stages and size were also affected. At 5 and 20 ng/ml hTNF-alpha, lactate production diminished on day 3 up to day 5, while glucose uptake increased on day 5. At 40 ng/ml, glucose uptake diminished on day 1 up to day 3, while ATP accumulation was detected on day 5. No significant changes in mRNA expression were detected in any of the treatments. We found that crosstalk involving hTNF-alpha and parasite signaling plays a role in the fine-scale regulation of the worm's metabolism and physiology, and points to new strategies for disease control. (AU)

• FAPESP's process: 12/50115-6 - Study of signal transduction pathways in Schistosoma mansoni and their relevance in the host-pathogen interaction (SchistoSig)
• Grantee: Katia Cristina Pereira Oliveira Santos
• Support Opportunities: Research Grants - Young Investigators Grants