Leptospira interrogans outer membrane protein LipL21 is a potent inhibitor of neutrophil myeloperoxidase

Author(s)

Vieira, Monica L. ^{[1, 2]} ; Teixeira, Aline F. ^[1] ; Pidde, Giselle ^[3] ; Ching, Ana T. C. ^[3] ; Tambourgi, Denise V. ^[3] ; Nascimento, Ana Lucia T. O. ^[1] ; Herwald, Heiko ^[2]

Affiliation

^[1] Inst Butantan, Ctr Biotecnol, Ave Vital Brazil, Sao Paulo, SP - Brazil

^[2] Lund Univ, Div Infect Med, Dept Clin Sci, Lund - Sweden

^[3] Inst Butantan, Lab Imunoquim, Ave Vital Brazil, Sao Paulo, SP - Brazil

• Document type: Journal article
• Source: VIRULENCE; v. 9, n. 1, p. 414-425, 2018.
• Web of Science Citations: 3

Abstract

Leptospirosis is a widespread zoonotic and neglected infectious disease of human and veterinary concern that is caused by pathogenic Leptospira species. After entrance in the host, pathogenic leptospires evade the host natural defense mechanisms in order to propagate and disseminate to multiple organs. Myeloperoxidase is an enzyme stored in neutrophils azurophilic granules, and is released upon neutrophil activation to produce mainly hypochlorous acid, a strong oxidant and potent antimicrobial agent. In the present investigation, we studied the modulation of myeloperoxidase activity by L. interrogans serovar Copenhageni. We show that leptospires and their culture supernatants are able to inhibit both peroxidase and chlorination activities of myeloperoxidase, without interfering with neutrophil degranulation. By leptospiral outer membrane protein extraction and fractionation, we identified the proteins LipL21 and LipL45 as myeloperoxidase inhibitors, constituting new Leptospira virulence factors. Accordingly, we propose a function for the protein LipL21, one of the most expressed leptospiral outer membrane proteins. Our results show a novel innate immune evasion mechanism by which leptospires interfere with the host response in order to cope with the host oxidative stress and efficiently achieve dissemination and colonization. (AU)

• FAPESP's process: 14/50981-0 - Search for surface proteins among the genome sequences of Leptospira interrogans: functional and immunological characterization to understanding mechanisms involved in the bacterial pathogenesis
• Grantee: Ana Lucia Tabet Oller do Nascimento
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 14/18337-4 - Modulação da coagulação e inflamação do hospedeiro por Leptospira
• Grantee: Mônica Larucci Vieira
• Support Opportunities: Scholarships abroad - Research Internship - Post-doctor