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Mechanisms of complement evasion by Leptospira spp: Interaction of Leptospira with C1 inhibitor and C4b-binding protein

Grant number: 11/14347-7
Support Opportunities:Scholarships in Brazil - Master
Effective date (Start): March 01, 2012
Effective date (End): December 31, 2013
Field of knowledge:Biological Sciences - Immunology - Immunochemistry
Principal Investigator:Lourdes Isaac
Grantee:Leandro Carvalho Dantas Breda
Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

The complement system (CS) is responsible for killing microorganisms due to opsonization, phagocytosis and formation of membrane attack complex (MAC). CS also contributes to inflammation by generating C3a and C5a anaphylatoxins; releasing chemotactic factors and clearance of soluble immune complexes. This system is composed by more than 40 proteins, including regulatory proteins that avoid the activation of CS, cellular lyses and inflammation of host cells. However, pathogens may acquire host regulators of CS as a mechanism to evade and survive to immune system. Spirochete Leptospira cause leptospirosis disease. This pathogen can evade CS by interacting with complement regulatory proteins such as Factor H and C4b-binding protein (C4BP). Our main purpose is to investigate interactions between Leptospira spp membrane proteins and C1 inhibitor - an important regulator of classical and lectin pathways. We also will try to elucidate the interactions of "Short Consensus Repeats" (SCR) domains of C4BP and Leptospira.

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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)
BREDA, LEANDRO C. D.; HSIEH, CHING-LIN; CASTIBLANCO VALENCIA, MONICA M.; DA SILVA, LUDMILA B.; BARBOSA, ANGELA S.; BLOM, ANNA M.; YUNG-FU, CHANG; ISAAC, LOURDES. Fine Mapping of the Interaction between C4b-Binding Protein and Outer Membrane Proteins LigA and LigB of Pathogenic Leptospira interrogans. PLoS Neglected Tropical Diseases, v. 9, n. 10, . (11/14347-7, 10/50043-0)
DANTAS BREDA, LEANDRO CARVALHO; VASCONCELLOS, SILVIO ARRUDA; VASCONCELOS, DEWTON DE MORAES; ISAAC, LOURDES. Binding of human complement C1 sterase inhibitor to Leptospira spp.. Immunobiology, v. 223, n. 2, p. 183-190, . (11/14347-7, 15/09972-0)
Academic Publications
(References retrieved automatically from State of São Paulo Research Institutions)
BREDA, Leandro Carvalho Dantas. Immune evasion mechanisms by Leptospiras spp.: interaction with C1 esterase inhibitor and C4b-binding protein.. 2014. Master's Dissertation - Universidade de São Paulo (USP). Instituto de Ciências Biomédicas (ICB/SDI) São Paulo.

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