Complement system and Leptospirosis: understanding the role of C3 in renal fibrosis induced by chronic infection of pathogenic leptospires in murine experimental model

Abstract

Leptospirosis is an important zoonosis caused by bacteria of the genus Leptospira. It is present especially in developing and tropical or mild climate countries. Approximately one million cases are reported each year, of which about 10% progress to death. The contact of water and soil with contaminated urine, mainly rodents, is amplified in conditions of inadequate sanitation and/or flooding. The infected individual may be asymptomatic, present mild symptoms or develop more severe forms of Leptospirosis such as Weil's syndrome, presenting jaundice, renal failure and internal bleeding, which can lead to renal failure and hepatic failure. Chronic kidney disease is a pathology caused by renal fibrosing, leading to overload of the remaining nephrons and consequent kidney failure. It is known that Leptospirosis is able to lead to renal fibrosis, although some mechanisms have not yet been clarified. Leptospires activate the innate and adaptive immune response, such as: phagocytosis, generation of specific antibodies and activation of the complement system, among other biological functions. The complement system is part of the innate and adaptive immunity, being one of the first forms of defense of the host against pathogens. Once activated, chemotactic factors are generated, attracting inflammatory cells to the site. Formation of the membrane attack complex on the surface of the pathogen may cause its lysis. The deposition of C3b on the surface of the pathogen and other opsonins facilitates phagocytosis. The production of anaphylatoxins (C3a and C5a) also allows the release of inflammatory mediators of mast cells and basophils. With the activation of this system, the production of specific antibodies is stimulated, giving greater protection to the host.Previous results from our laboratory suggest that C3 deficient C57Black/6J mice develop interstitial nephritis after two weeks of infection, while wild mice do not exhibit this pathology. The objective of this project is to understand the role of the C3 component, the key protein of the complement system, during renal fibrosis caused by chronic leptospire infection. (AU)