title: Immune evasion by pathogenic Leptospira strains: the secretion of proteases that directly cleave complement proteins.
abstract: Leptospirosis is an infectious disease of public health importance. To successfully colonize the host, pathogens have evolved multiple strategies to escape the complement system. Here we demonstrate that the culture supernatant of pathogenic but not saprophytic Leptospira inhibit the three complement pathways. We showed that the proteolytic activity in the supernatants of pathogenic strains targets the central complement molecule C3 and specific proteins from each pathway, such as factor B, C2, and C4b. The proteases cleaved α and β chains of C3 and work in synergy with host regulators to inactivate C3b. Proteolytic activity was inhibited by 1,10-phenanthroline, suggesting the participation of metalloproteases. A recombinant leptospiral metalloprotease from the thermolysin family cleaved C3 in serum and could be one of the proteases responsible for the supernatant activity. We conclude that pathogenic leptospiral proteases can deactivate immune effector molecules and represent potential targets to the development of new therapies in leptospirosis.
authors.affiliation: Department of Immunology, Institute of Biomedical Sciences.
authors.forename: Tatiana Rodrigues
authors.initials: TR
authors.lastname: Fraga
authors.forename: Daniella Dos Santos
authors.initials: Ddos S
authors.lastname: Courrol
authors.forename: Mónica Marcela
authors.initials: MM
authors.lastname: Castiblanco-Valencia
authors.forename: Izaura Yoshico
authors.initials: IY
authors.lastname: Hirata
authors.forename: Sílvio Arruda
authors.initials: SA
authors.lastname: Vasconcellos
authors.forename: Luiz
authors.initials: L
authors.lastname: Juliano
authors.forename: Angela Silva
authors.initials: AS
authors.lastname: Barbosa
authors.forename: Lourdes
authors.initials: L
authors.lastname: Isaac
mesh_terms: D001426:Bacterial Proteins / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism*; D003176:Complement C3 / Q000378:metabolism*; D003171:Complement Pathway, Classical; D006801:Humans; D057131:Immune Evasion; D007919:Leptospira / Q000737:chemistry / Q000201:enzymology / Q000276:immunology* / Q000472:pathogenicity; D007922:Leptospirosis / Q000276:immunology / Q000382:microbiology*; D008954:Models, Biological; D010447:Peptide Hydrolases / Q000276:immunology / Q000302:isolation & purification / Q000378:metabolism*; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D013820:Thermolysin / Q000737:chemistry / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D003176:Complement C3; D011994:Recombinant Proteins; D010447:Peptide Hydrolases; D013820:Thermolysin
keywords: Complement System; Immune Evasion; Innate Immunity; Leptospira; Leptospirosis; Proteases