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Schistosomiasis: Host-Parasite interactions

Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Immunol. | doi: 10.3389/fimmu.2019.00021

SMP38 MAP KINASE REGULATION IN SCHISTOSOMA MANSONI: ROLES IN SURVIVAL, OVIPOSITION AND PROTECTION AGAINST OXIDATIVE STRESS

Lívia d. Avelar1,  Sandra G. Gava1,  Renata H. Neves2,  Mercedes C. Da Silva1, Neusa Araújo1,  Naiara C. Tavares1,  Assmaa E. Khal1, Ana Carolina A. Matos1, José R. Machado-Silva2,  Guilherme C. Oliveira3* and  Marina M. Mourão1*
  • 1Fiocruz Research Center Renê Rachou, Brazil
  • 2Rio de Janeiro State University, Brazil
  • 3Instituto Tecnológico Vale (ITV), Brazil

Eukaryotic protein kinases (ePKs) are good medical targets for drug development in different biological systems. ePKs participate in many cellular processes, including the p38 MAPK regulation of homeostasis upon oxidative stress. We propose to assess the role of Smp38 MAPK signaling pathway in S. mansoni development and protection against oxidative stress, parasite survival, and also to elucidate which target genes have their expression regulated by Smp38 MAPK. After a significant reduction of up to 84% in the transcription level by Smp38 MAPK gene knockdown, no visible phenotypic changes were reported in schistosomula in culture. The development of adult worms was tested in vivo in mice infected with the Smp38 knocked-down schistosomula. It was observed that Smp38 MAPK has an essential role in the transformation and survival of the parasites as a low number of adult worms was recovered. Smp38 knockdown also resulted in decreased egg production, damaged adult worm tegument, and underdeveloped ovaries in females. Furthermore, only ~13% of the eggs produced developed into mature eggs. Our results suggest that inhibition of the Smp38 MAPK activity interfere in parasites protection against reactive oxygen species. Smp38 knockdown in adult worms resulted in 80% reduction in transcription levels on the 10th day, with consequent reduction of 94.4% in oviposition in vitro. In order to search for Smp38 MAPK pathway regulated genes, we used an RNASeq approach and identified 1,154 DEGs in Smp38 knockdown schistosomula. A substantial proportion of DEGs encode proteins with unknown function. The results indicate that Smp38 regulates essential signaling pathways for the establishment of parasite homeostasis, including genes related to antioxidant defense, structural composition of ribosomes, spliceosomes, cytoskeleton, as well as, purine and pyrimidine metabolism pathways. Our data show that the Smp38 MAPK signaling pathway is a critical route for parasite development and may present attractive therapeutic targets for the treatment and control of schistosomiasis.

Keywords: Schistosoma mansoni, P38 MAP kinase, Signaling Pathways, Oogenesis, development, Oxidative Stress, Gene Expression

Received: 17 Oct 2018; Accepted: 07 Jan 2019.

Edited by:

Thiago Almeida Pereira, Institute for Stem Cell Biology and Regenerative Medicine, Stanford University, United States

Reviewed by:

Colette Dissous, Institut National de la Santé et de la Recherche Médicale (INSERM), France
RONALDO D. AUGUSTO, Centre National de la Recherche Scientifique (CNRS), France  

Copyright: © 2019 Avelar, Gava, Neves, Da Silva, Araújo, Tavares, Khal, Matos, Machado-Silva, Oliveira and Mourão. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence:
MD, PhD. Guilherme C. Oliveira, Instituto Tecnológico Vale (ITV), Belém, Pará, Brazil, guilherme.oliveira@itv.org
MD, PhD. Marina M. Mourão, Fiocruz Research Center Renê Rachou, Belo Horizonte, Minas Gerais, Brazil, mourao.marina@gmail.com