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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Heparin-Binding Protein Release Is Strongly Induced by Leptospira Species and Is a Candidate for an Early Diagnostic Marker of Human Leptospirosis

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Author(s):
Vieira, Monica L. [1, 2] ; Persson, Sandra [1] ; Lopes-Ferreira, Monica [3] ; Romero, Eliete C. [4] ; Kirchgatter, Karin [5] ; Nascimento, Ana Lucia T. O. [2] ; Herwald, Heiko [1]
Total Authors: 7
Affiliation:
[1] Lund Univ, Div Infect Med, Dept Clin Sci, Lund - Sweden
[2] Inst Butantan, Lab Especial Desenvolvimento Vacinas, Sao Paulo - Brazil
[3] Inst Butantan, Lab Especial Toxinol Aplicada, Sao Paulo - Brazil
[4] Adolfo Lutz Inst, Ctr Bacteriol, Sao Paulo - Brazil
[5] Univ Sao Paulo, Inst Med Trop Sao Paulo, Superintendencia Controle Endemias, Nucleo Estudos Malaria, Sao Paulo - Brazil
Total Affiliations: 5
Document type: Journal article
Source: Journal of Infectious Diseases; v. 219, n. 6, p. 996-1006, MAR 15 2019.
Web of Science Citations: 0
Abstract

Here we show that heparin-binding protein (HBP) can be used as an early biomarker in patients with leptospirosis. Our experiments further suggest that leptospiral proteins are able to release HBP to an extent that the vascular barrier is impaired.Leptospirosis, caused by spirochetes of the genus Leptospira, is one of the most widespread zoonoses worldwide. Efficient diagnostic methods for early diagnosis of leptospirosis are still lacking, and acute disease presents with nonspecific symptomatology and is often misdiagnosed. The leptospires pathogenic processes and virulence mechanisms remain virtually unknown. In severe infections, hemostatic impairment is frequently observed, and pathophysiological complications often develop when the host response is modulated by the pathogen. The neutrophil heparin-binding protein (HBP) is an inflammatory mediator and potent inducer of vascular leakage. In this study, we found that leptospires and their secreted products induce the release of HBP from stimulated neutrophils through a controlled degranulation mechanism. We acknowledged 2 leptospiral proteins as able to induce HBP degranulation. These findings have clinical implications, as high levels of HBP were detected in serum from patients with leptospirosis, especially at the early phase of the disease. In conclusion, we describe a new mechanism by which the leptospirosis pathophysiological complications may arise, such as vascular leakage and edema formation. We also propose HBP as a new early screening biomarker for human leptospirosis. (AU)

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
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: 18/07054-2 - Platelets at the interface of immunity, inflammation and hemostasis modulation in leptospirosis
Grantee:Mônica Larucci Vieira
Support Opportunities: Scholarships in Brazil - Young Researchers