Modulação da coagulação e inflamação do hospedeiro por Leptospira

• Grant number: 14/18337-4
• Support Opportunities: Scholarships abroad - Research Internship - Post-doctor
• Start date: February 01, 2015
• End date: January 31, 2016
• Field of knowledge: Biological Sciences - Microbiology
• Principal Investigator: Ana Lucia Tabet Oller do Nascimento
• Grantee: Mônica Larucci Vieira
• Supervisor: Heiko Herwald
• Host Institution: Instituto Butantan. Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil
• Institution abroad: Lund University, Lund, Sweden
• Associated to the scholarship: 12/50523-7 - Cloning, expression, purification and characterization of Leptospira interrogans thermolysin: interactions with plasminogen / plasmin system and implications for infection, BP.PD

Abstract

The innate immunity combines a number of early host defense responses that are essential for defeating microbial infections. However, during systemic progression of the disease, an overstimulation of the innate immune system may occur that eventually leads to severe pathological conditions. Clinical symptoms of patients suffering from bacterial infections are a culmination of complex interactions between the infecting microorganism and host immune responses, including the induction of systemic activation of the coagulation system, impaired fibrinolysis, and exaggerated inflammatory reactions. In severe infections, hemostatic impairment like coagulation/fibrinolysis dysfunction, vascular leakage, and pathological cytokine levels are frequently observed. These complications often occur when the host response is controlled and/or modulated by the bacterial pathogen. There are some evidences suggesting that during the infection caused by the bacterial pathogen Leptospira, the hemostatic equilibrium of the host is compromised. We have previously demonstrated that Leptospira interferes with the host's fibrinolytic system. In the present investigation, we aim to further analyze the mechanisms by which this pathogen interacts with the host during infection. In particular, it is intended to study the mechanisms that lead to the stimulation of immune cells and to the activation of procoagulant activity either due to contact system activation or due to the induction of tissue factor by bacteria. The results obtained from these investigations will contribute to the understanding of the leptospirosis pathophysiological mechanisms, opening new routes for development of diagnostic tools and the discovery of novel treatments in the severe manifestations of the disease. (AU)

Scientific publications

(5)

(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)

SILVA, LUCAS P.; FERNANDES, LUIS G. V.; VIEIRA, MONICA L.; DE SOUZA, GISELE O.; HEINEMANN, MARCOS B.; VASCONCELLOS, SILVIO A.; ROMERO, ELIETE C.; NASCIMENTO, ANA L. T. O.. Evaluation of two novel leptospiral proteins for their interaction with human host components. PATHOGENS AND DISEASE, v. 74, n. 5, JUL 2016. (14/50981-0, 14/18337-4, 12/23913-9, 12/24164-0)

VIEIRA, MONICA L.; NAUDIN, CLEMENT; MORGELIN, MATTHIAS; ROMERO, ELIETE C.; NASCIMENTO, ANA LUCIA T. O.; HERWALD, HEIKO. Modulation of Hemostatic and Inflammatory Responses by Leptospira Spp.. PLoS Neglected Tropical Diseases, v. 10, n. 5, MAY 2016. (14/18337-4)

VIEIRA, MONICA L.; TEIXEIRA, ALINE F.; PIDDE, GISELLE; CHING, ANA T. C.; TAMBOURGI, DENISE V.; NASCIMENTO, ANA LUCIA T. O.; HERWALD, HEIKO. Leptospira interrogans outer membrane protein LipL21 is a potent inhibitor of neutrophil myeloperoxidase. VIRULENCE, v. 9, n. 1, p. 414-425, 2018. (14/50981-0, 14/18337-4)

SIQUEIRA, GABRIELA H.; TEIXEIRA, ALINE F.; FERNANDES, LUIS G.; DE SOUZA, GISELE O.; KIRCHGATTER, KARIN; ROMERO, ELIETE C.; VASCONCELLOS, SILVIO A.; VIEIRA, MONICA L.; NASCIMENTO, ANA LUCIA T. O.. The recombinant LIC10508 is a plasma fibronectin, plasminogen, fibrinogen and C4BP-binding protein of Leptospira interrogans. PATHOGENS AND DISEASE, v. 74, n. 2, MAR 2016. (12/23913-9, 12/01797-7, 12/50523-7, 14/18337-4, 14/03792-8, 12/24164-0)

VIEIRA, MONICA L.; PERSSON, SANDRA; LOPES-FERREIRA, MONICA; ROMERO, ELIETE C.; KIRCHGATTER, KARIN; NASCIMENTO, ANA LUCIA T. O.; HERWALD, HEIKO. Heparin-Binding Protein Release Is Strongly Induced by Leptospira Species and Is a Candidate for an Early Diagnostic Marker of Human Leptospirosis. Journal of Infectious Diseases, v. 219, n. 6, p. 996-1006, MAR 15 2019. (14/18337-4, 14/50981-0, 18/07054-2)