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Evaluation of the molecular mechanisms involved in the modulation of immune response by high molecular weight components of Ascaris suum, crotoxin and Phospholipase A2 from Crotalus durissus terrificus venom

Grant number: 15/15608-0
Support type:Regular Research Grants
Duration: April 01, 2016 - June 30, 2018
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

Abstract

The characterization of the mechanisms involved in the immunomodulation exerted by distinct molecules is relevant to the development of new therapeutic agents. Secretory/excretory products from helminth are able to suppress the immune system to ensure its survival in the host. Our results showed that glycosylated high molecular weight antigens from Ascaris suum extract inhibit the dendritic cells maturation and then the T lymphocytes activation. This modulatory effect on dendritic cells is dependent of C-type lectin receptors. The inhibitory action of glycoconjugates from distinct helminths on dendritic cells has been evaluated, however the molecular pathways involved in this process are poorly understood. Therefore, we aim to study the signaling pathways triggered by the recognition of these Ascaris antigens by C-type lectin receptors. Furthermore, we aim to evaluate the effect of these antigens in the intracellular activation of dendritic cells incubated with a pro-inflammatory agent as lipopolysaccharide (LPS). For this, we propose to analyze the phosphorylation of some intracellular proteins that regulate the activation or inhibition of dendritic cells activities. In addition of this, we aim to study the immunomodulatory effect of crotoxin and its phospholipase A2 subunit isolated from the Crotalus durissus terrificus venom. The crotoxin is the main component from the Crotalus durissus terrificus venom and is composed of CA and CB subunits, which the last one is a phospholipase A2 (PLA2). We showed that crotoxin inhibits the immune response anti-human serum albumin and experimental colitis. As the crotoxin, the phospholipase A2 subunit inhibits the dendritic cells activation induced by LPS and also induces the production of lipid mediators as prostaglandin E2 and lipoxin A4. Therefore, we aim to evaluate the effect of crotoxin and PLA2 on DCs as well as on the T cell differentiation. It will be analyzed the expression of molecules involved in the induction of tolerance or activation and differentiation of T cells. Furthermore, it will be studied the soluble mediators involved in this process. We also intend to evaluate the T lymphocytes profile generated by the contact with the dendritic cells incubated with crotoxin or PLA2. We intend with this study to contribute with new insights about the mechanisms involved in the modulation of innate and adaptive immunity exerted by Ascaris antigens, crotoxin and PLA2. (AU)

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)
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.

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