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

Vieira, Mônica L. LU ; Persson, Sandra LU ; Lopes-Ferreira, Mônica; Romero, Eliete C.; Kirchgatter, Karin; Nascimento, Ana Lucia T.O. and Herwald, Heiko LU (2019) In The Journal of infectious diseases 219(6). p.996-1006
Abstract

BACKGROUND: 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. RESULTS: In this study, we found that leptospires and their secreted products... (More)

BACKGROUND: 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. RESULTS: 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. CONCLUSION: 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.

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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Leptospira, host-pathogen-interactions, infection, inflammation, neutrophils
in
The Journal of infectious diseases
volume
219
issue
6
pages
11 pages
publisher
Oxford University Press
external identifiers
  • scopus:85062001599
ISSN
1537-6613
DOI
10.1093/infdis/jiy589
language
English
LU publication?
yes
id
1612b699-d0d7-4a04-ac6d-cfb6ddfb8129
date added to LUP
2019-03-06 10:42:36
date last changed
2019-09-04 02:21:17
@article{1612b699-d0d7-4a04-ac6d-cfb6ddfb8129,
  abstract     = {<p>BACKGROUND: 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. RESULTS: 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. CONCLUSION: 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.</p>},
  author       = {Vieira, Mônica L. and Persson, Sandra and Lopes-Ferreira, Mônica and Romero, Eliete C. and Kirchgatter, Karin and Nascimento, Ana Lucia T.O. and Herwald, Heiko},
  issn         = {1537-6613},
  keyword      = {Leptospira,host-pathogen-interactions,infection,inflammation,neutrophils},
  language     = {eng},
  number       = {6},
  pages        = {996--1006},
  publisher    = {Oxford University Press},
  series       = {The Journal of infectious diseases},
  title        = {Heparin-Binding Protein Release Is Strongly Induced by Leptospira Species and Is a Candidate for an Early Diagnostic Marker of Human Leptospirosis},
  url          = {http://dx.doi.org/10.1093/infdis/jiy589},
  volume       = {219},
  year         = {2019},
}