Secretion of proteases by leptospires and phagocytosis inhibition

• Grant number: 23/01123-0
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: April 01, 2023
• End date: July 31, 2025
• Field of knowledge: Biological Sciences - Immunology - Immunochemistry
• Principal Investigator: Lourdes Isaac
• Grantee: Luana Barbosa Rodrigues dos Santos
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Leptospirosis is a zoonosis caused by bacteria from the genus Leptospira and is transmitted by direct or indirect contact with the urine of infected animals. The main reservoirs are rats (Rattus norvegicus and Rattus rattus), but other rodents and mammals are also included. The symptoms have a broad spectrum, from asymptomatic cases to severe clinical complications that include organ failure and lung hemorrhagic syndrome, which can lead to death in a short period of time. Differently from saprophytic leptospires, pathogenic species are capable of surviving for long periods in the host because of refined immune evasion mechanisms, which allow an efficient escape from the Complement System. The Complement is a group of plasmatic proteins that can be activated by three different pathways and has as its main functions the (i) opsonization of pathogens, (ii) release of chemotactic fragments and (iii) formation of the membrane attack complex (MAC), responsible for bacterial lysis. However, pathogenic species like L. interrogans are able to secrete proteases like thermolysin and leptoplysin that cleave C3, the central Complement molecule, and its fragments C3b and iC3b, providing strong inhibition of the Complement pathways, of opsonization and formation of MAC. In that light, this work aims to analyze the damage of the Complement function that those proteases cause, observing the phagocytosis by THP-1 cells of zymosan particles in the absence and presence of different concentrations of the bacterial proteases.