Leptospira-host interaction: aspects related to tissue invasion and innate immune system evasion

Abstract

Leptospirosis, caused by spirochetes of the genus Leptospira, is a zoonosis of worldwide distribution. Highly frequent in tropical and subtropical areas, the disease represents an important public health problem. Pathogenic leptospires have the ability to escape the natural defense mechanisms of the body by circumventing complement mediated lysis. They also express a number of membrane proteins capable of interacting with extracellular matrix molecules and host cells. Moreover, leptospires acquire human plasminogen to their surfaces, which is converted to its active form, plasmin. Recent data by our group indicate that proteins secreted by Leptospira pathogenic species cleave several human complement proteins, rendering them inactive. Our group research is focused on the identification of invasion mechanisms as well as of immune evasion strategies employed by pathogenic leptospires. The main goals of this project are: identification of Leptospira proteases involved in the degradation of extracellular matrix and coagulation cascade molecules (subproject # 1) and evaluation of the relevance of the interaction of vitronectin with leptospiral outer membrane proteins (subproject # 2). The identification and the characterization of proteases that degrade ECM molecules and of bacterial surface proteins involved in the interaction with negative complement regulators is of great relevance, contributing to the development of therapeutic and/or preventive strategies that may interfere with invasion and tissue destruction observed in leptospirosis as well as in the immune evasion mechanism presented by this pathogen. (AU)