Platelets at the interface of immunity, inflammation and hemostasis modulation in leptospirosis

• Grant number: 17/00236-5
• Support type: Research Grants - Young Investigators Grants
• Duration: April 01, 2018 - September 30, 2019
• Field of knowledge: Interdisciplinary Subjects
• Principal researcher: Mônica Larucci Vieira
• Grantee: Mônica Larucci Vieira
• Home Institution: Instituto Butantan. Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil
• Assoc. researchers: Ana Lucia Tabet Oller do Nascimento ; Marcos Bryan Heinemann
• Associated scholarship(s): 18/07054-2 - Platelets at the interface of immunity, inflammation and hemostasis modulation in leptospirosis, BP.JP

Abstract

Leptospirosis is an important zoonosis, caused by spirochete bacteria of the genus Leptospira. Despite its importance and recent functional genomics studies, the molecular mechanisms of the infectious process and the pathophysiology of leptospirosis remain unclear. However, increasing evidence suggests that pathogen over-stimulation and/or modulation of immune response and host inflammation, as well as haemostatic balance disturbance, appear to play a central role in the pathogenesis and symptomatology of the disease. Platelets have a major function in primary hemostasis. In addition, platelets have numerous activities, being inflammatory cells with multiple roles ranging from innate immune responses to adaptive immunity. The immuno-inflammatory regulatory functions of platelets are relatively new concepts within bacterial infections, and still unexplored in leptospirosis. Thus, this project proposes the study of platelet activation and its interactions with other immune cells and effector or regulatory molecules as a mechanism host response modulation during Leptospira infection. The main objective is the identification of immunological, inflammatory and haemostatic molecular mechanisms causing severe symptoms such as hemorrhages, vasculitis and organ failure in leptospirosis. These studies could constitute a basis for the development of new therapeutic, diagnostic and prophylactic strategies against the disease. (AU)

Scientific publications

(7)

(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, G. M.; BERTO, D. H.; LIMA, C. A.; WAITMAN, K. B.; LIMA, C. F. G.; PREZOTO, B. C.; VIEIRA, M. L.; ROCHA, M. M. T.; GONCALVES, L. R. C.; ANDRADE, S. A.. Synergistic effect of serine protease inhibitors and a bothropic antivenom in reducing local hemorrhage and coagulopathy caused by Bothrops jararaca venom. Toxicon, v. 199, p. 87-93, AUG 2021. (17/00236-5, 13/07467-1, 17/04321-7)

TEIXEIRA, ALINE F.; FERNANDES, V, LUIS G.; CAVENAGUE, MARIA F.; TAKAHASHI, MARIA B.; SANTOS, JADEMILSON C.; PASSALIA, FELIPE J.; DAROZ, BRENDA B.; KOCHI, LEANDRO T.; VIEIRA, MONICA L.; NASCIMENTO, ANA L. T. O.. Adjuvanted leptospiral vaccines: Challenges and future development of new leptospirosis vaccines. Vaccine, v. 37, n. 30, p. 3961-3973, JUL 9 2019. (17/25167-6, 17/01102-2, 16/11541-0, 17/26223-7, 14/50981-0, 17/06731-8, 17/01411-5, 17/00236-5, 16/01384-5)

VIEIRA, MONICA L.; HERWALD, HEIKO; NASCIMENTO, ANA LUCIA T. O.. The interplay between host haemostatic systems and Leptospira spp. infections. CRITICAL REVIEWS IN MICROBIOLOGY, v. 46, n. 2, MAR 2020. (17/00236-5, 14/50981-0)

PASSALIA, FELIPE JOSE; CARVALHO, ENEAS; HEINEMANN, MARCOS BRYAN; VIEIRA, MONICA LARUCCI; NASCIMENTO, ANA LUCIA T. O.. The Leptospira interrogans LIC10774 is a multifunctional surface protein that binds calcium and interacts with host components. MICROBIOLOGICAL RESEARCH, v. 235, MAY 2020. (17/00236-5, 14/50981-0, 17/01102-2, 18/07054-2)

TAKAHASHI, M. B.; TEIXEIRA, A. F.; ALTO, NASCIMENTO. The leptospiral LipL21 and LipL41 proteins exhibit a broad spectrum of interactions with host cell components. VIRULENCE, v. 12, n. 1, p. 2798-2813, DEC 31 2021. (17/26223-7, 19/17488-2, 17/00236-5)

PASSALIA, FELIPE JOSE; HEINEMANN, MARCOS BRYAN; DE ANDRADE, SONIA APARECIDA; NASCIMENTO, ANA LUCIA T. O.; VIEIRA, MONICA LARUCCI. Leptospira interrogans Bat proteins impair host hemostasis by fibrinogen cleavage and platelet aggregation inhibition. MEDICAL MICROBIOLOGY AND IMMUNOLOGY, v. 209, n. 2, FEB 2020. (17/01102-2, 18/07054-2, 17/00236-5)

PASSALIA, FELIPE JOSE; HEINEMANN, MARCOS BRYAN; VIEIRA, MONICA LARUCCI; NASCIMENTO, ANA LUCIA T. O.. A Novel Leptospira interrogans Protein LIC13086 Inhibits Fibrin Clot Formation and Interacts With Host Components. FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY, v. 11, JUL 1 2021. (17/01102-2, 18/07054-2, 17/00236-5, 14/50981-0, 19/17488-2)