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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art_VIEIRA_HeparinBinding_Protein_Release_Is_Strongly_Induced_by_Leptospira_2019.PDF (9.28 MB)
Citações na Scopus
5
Tipo de produção
article
Data de publicação
2019
DOI
Scopus
Web of Science
PubMed
Título da Revista
ISSN da Revista
Título do Volume
Editora
OXFORD UNIV PRESS INC
Autores
VIEIRA, Monica L.
PERSSON, Sandra
LOPES-FERREIRA, Monica
ROMERO, Eliete C.
NASCIMENTO, Ana Lucia T. O.
HERWALD, Heiko
Citação
JOURNAL OF INFECTIOUS DISEASES, v.219, n.6, p.996-1006, 2019
Projetos de Pesquisa
Unidades Organizacionais
Fascículo
Resumo
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.
Palavras-chave
Leptospira, inflammation, infection, neutrophils, host-pathogen-interactions
URI
https://observatorio.fm.usp.br/handle/OPI/32031
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Coleções
Artigos e Materiais de Revistas Científicas - IMT
Artigos e Materiais de Revistas Científicas - LIM/49