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Mechanisms involved in the modulation of the immune response induced by high molecular weight components of Ascaris suum extract and crotoxin isolated from Crotalus durissus terrificus venom

Grant number: 11/23735-0
Support type:Regular Research Grants
Duration: July 01, 2012 - June 30, 2014
Field of knowledge:Biological Sciences - Immunology - Cellular Immunology
Principal Investigator:Eliana Faquim de Lima Mauro
Grantee:Eliana Faquim de Lima Mauro
Home Institution: Instituto Butantan. Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil
Assoc. researchers:Irene Fernandes ; Jacqueline de Fátima Jacysyn ; Niels Olsen Saraiva Câmara

Abstract

The identification/characterization of immunomodulatory molecules as well the mechanisms involved in their effect have been the focus of numerous studies, since they may represent alternative tools in the treatment of diseases or immunological disorders as autoimmune diseases, chronic inflammation among others. Helminth infections as Ascaris suum (Asc) and their secreted antigens induce an immunosuppresion state in the host. Immunomodulatory effect has also been observed with the Crotalus durissus terrificus (C.d.terrificus) rattlesnake venom and its main toxin, the crotoxin (CTX). We verified that the Asc extract and its high molecular weight components (PI) inhibit the anti-ovalbumin (OVA) response. The PI antigens modulate the ability of antigen-presenting cells (APCs), such as dendritic cells (DCs), to activate TCD4+ lymphocytes, via IL-10. Furthermore, the TLR2 and 4 are not involved in immunomodulation exerted by PI. About the modulatory effect of the CTX from C.d.terrificus, we verified that is not mediated by cell death by apoptosis and/or necrosis. The CTXmodulates the humoral and cellular responses in vivo, inhibits the MHC class II and costimulatory molecules expression on APCs and induces IL-10, TGF-² and PGE2 secretion in mice suggesting an immunomodulatory environment. Therefore, the aim of this project is to study the mechanisms involved in the PI and CTX effect. We will evaluate the role of C-type lectin receptors (CLRs) in the recognition of PI antigens by DCs and thus the immunoregulation exerted by them. For the CTX, we will study its effect on DCs and as well the T lymphocytes activation in vitro. The results may provide relevant information to clarify the mechanisms involved in immunomodulation exerted by these components. (AU)

Scientific publications (4)
(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)
FREITAS, A. P.; FAVORETTO, B. C.; CLISSA, P. B.; SAMPAIO, S. C.; FAQUIM-MAURO, E. L. Crotoxin Isolated from Crotalus durissus terrificus Venom Modulates the Functional Activity of Dendritic Cells via Formyl Peptide Receptors. JOURNAL OF IMMUNOLOGY RESEARCH, 2018. Web of Science Citations: 3.
FAVORETTO, BRUNA C.; CASABUONO, ADRIANA A. C.; PORTES-JUNIOR, JOSE A.; JACYSYN, JACQUELINE F.; COUTO, ALICIA S.; FAQUIM-MAURO, ELIANA L. High molecular weight components containing N-linked oligosaccharides of Ascaris suum extract inhibit the dendritic cells activation through DC-SIGN and MR. Molecular Immunology, v. 87, p. 33-46, JUL 2017. Web of Science Citations: 6.
ALMEIDA, CAROLINE DE SOUZA; ANDRADE-OLIVEIRA, VINICIUS; SARAIVA CAMARA, NIELS OLSEN; JACYSYN, JACQUELINE F.; FAQUIM-MAURO, ELIANA L. Crotoxin from Crotalus durissus terrificus Is Able to Down-Modulate the Acute Intestinal Inflammation in Mice. PLoS One, v. 10, n. 4 APR 8 2015. Web of Science Citations: 10.
FAVORETTO, BRUNA C.; SILVA, SANDRIANA R.; JACYSYN, JACQUELINE F.; CAMARA, NIELS O. S.; FAQUIM-MAURO, ELIANA L. TLR2-and 4-independent immunomodulatory effect of high molecular weight components from Ascaris suum. Molecular Immunology, v. 58, n. 1, p. 17-26, MAR 2014. Web of Science Citations: 4.

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