Complement System Activation in Experimental Leptospirosis-associated Pulmonary Hemorrhagic Syndrome in C3H/HeJ Mice

• Grant number: 23/01273-2
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: May 01, 2023
• End date: July 31, 2024
• Field of knowledge: Biological Sciences - Immunology - Immunochemistry
• Principal Investigator: Lourdes Isaac
• Grantee: Ana Carolina Mikejevs Lorga
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Leptospirosis is a neglected tropical disease caused by spirochetes of the genusLeptospira present on all continents. Contagion happens through direct or indirectcontact with soil or water contaminated with urine from chronically infected animals,usually rodents, with damaged skin or mucous membranes. Being of major medical andveterinary importance, the infection can be asymptomatic or expressed clinically in mildcases, similar to influenza, or severe, such as the development of Weil's syndrome andleptospirosis-associated pulmonary hemorrhagic syndrome (LPHS). The latter scenariocan rapidly progress to death within 72 hours after presenting the first symptoms,achieving a case fatality rate of up to approximately 50%. Characterized as part of boththe innate and acquired immune systems, the Complement System (CS) has threeactivation pathways which culminate in the formation of the Membrane AttackComplex (MAC), among other key functions in combating extracellular pathogens suchas Leptospira. Few studies examined the possible involvement of the CS in theetiopathogenesis of LPHS. To evaluate its role during LPHS, C3H/HeJ (TLR-4deficient) mice will be infected with Leptospira interrogans serovar Copenhageni andevaluated for CS activation in serum and characterization of the leukocyte population.Despite the high mortality and wide epidemiological scope of the disease, thepathogenesis of LPHS is still not well defined. Thus, studies that seek to understand itsetiopathogenesis are invaluable for better prognosis and identification of potentialtherapeutic targets in leptospirosis.