Identification of polymorphism of CFH gene in patients with leptospirosis

• Grant number: 17/18936-3
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: December 01, 2017
• End date: November 30, 2018
• Field of knowledge: Biological Sciences - Immunology - Immunogenetics
• Principal Investigator: Lourdes Isaac
• Grantee: Leonardo Moura Midon
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Leptospirosis is an important zoonosis especially in developing countries with tropical or mild climate. Approximately 1 million cases are reported each year, of which about 10 % progress to death. Inadequate sanitation and/or floods amplify the contact of water and soil with animal contaminated urine. These microorganisms are of extracellular life and activate the immune innate and adaptive responses, such as phagocytosis, generation of specific antibodies and activation of the Complement System, among other many biological functions. The Complement System is part of the innate and adaptive immunity, being one of the first in defense of the host against pathogens and is activated by the Classic Pathway, Alternative Pathway and/or Lectin Pathway. Once activated, they generate chemotactic factors, attracting inflammatory cells to the location of infection. The Membrane Attack Complex can cause the death of pathogens. The deposition of C3b and other opsonines on the pathogen surface facilitate phagocytosis. The production of anaphylotoxins (C3a, C4a and C5a) liberate inflammatory mediators from mast cells and basophils. With the activation of this system, the production of specific antibodies is stimulated, bringing more protection for the host. Factor H is one of the main regulating factors of Alternative Pathway and acts on the decay of C3-convertase, avoiding the amplification of this pathway with the consequent and exaggerated consume of C3 and avoiding attacks of the own host cells. LigA and LigB are surface proteins found on pathogenic leptospira and can interact with certain domains of the human Factor H, preventing the Alternative Pathway activation, thus contributing for its survival inside the host. Our working hypothesis is that mutations on the Factor H can lead to an increased interaction between this factor and leptospiras, facilitating its dissemination inside the host. The objective of this project is to identify the presence of polymorphisms of the CFH gene in patients with leptospirosis that favors a better interaction with pathogenic leptospira and that can correlate with severe cases of this disease. (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)

OKOCHI ALVES DA SILVA, PRISCILLA YURI; MIDON, LEONARDO MOURA; HEINEMANN, MARCOS BRYAN; VASCONCELOS, DEWTON DE MORAES; BARBOSA, ANGELA SILVA; ISAAC, LOURDES. Contribution of Complement System pathways to the killing of Leptospira spp.. Microbes and Infection, v. 22, n. 10, p. 550-557, NOV-DEC 2020. (17/12924-3, 17/18936-3)