Etiopathogeny of leptospirosis-associated hemorrhagic pulmonar syndrome: complement system and possible implications for an in vivo murine model

• Grant number: 21/14030-5
• Support Opportunities: Scholarships in Brazil - Master
• Start date: May 01, 2022
• End date: November 30, 2023
• Field of knowledge: Biological Sciences - Immunology - Cellular Immunology
• Principal Investigator: Lourdes Isaac
• Grantee: Lara Rodrigues da Silva
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Leptospirosis is considered an emerging and neglected disease caused by the pathogenic spirock bacteria of the leptospira gender. Contamination usually occurs by the direct contact of the mucosal or skin injured with the contaminated urine of rodents, cattle or domestic animals or indirectly by contact with contaminated water, soil or vegetation. Acute clinical symptoms of leptospirosis are commonly common to various other acute febrile diseases and lack of a necessary diagnosis the process of treatment of infected patients retarded. Infection may progress to a severe pulmonary hemorrhagic syndrome associated with leptospirosis (LPHS) in 5 to 10% of notified cases that generally die 72h after the first initiate of symptoms. Few experimental and post studies mortem in the lungs of patients with LPHS indicate the deposition of the C3 protein of the complement system and antibodies in the pulmonary tissue. Considering the potential inflammatory role arising from the uncontrolled activation of this system in the lung, we wish to study its importance in the LPHS in a murine model in vivo. C3H/HEJ mice will be infected with Leptospira Interrogans Sorovar ICTEROHAEMORHAGIAE strain 11435 and evaluated macroscopic and microscopically regarding the presence of pulmonary hemorrhage to confirm the LPHS. Subsequently, the deposition of C3C proteins, MASP-2, Bb fragment, C1q and the SC5B-9 complex in the lung of mice will be determined by immunohistochemistry. In this study, it is expected to improve the understanding of the host's immunological responses against leptospiras, to track possible complications and seek strategies for consequent therapeutic interventions more effective for leptospirosis. (AU)