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Leptospira interrogans outer membrane protein lipl21 is a potent inhibitor of neutrophil myeloperoxidase

Vieira, Monica L. LU ; Teixeira, Aline F.; Pidde, Giselle; Ching, Ana T.C.; Tambourgi, Denise V.; Nascimento, Ana Lucia T.O. and Herwald, Heiko LU (2018) In Virulence 9(1). p.414-425
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... (More)

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.

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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Host-pathogen interactions, Immune evasion, Innate immunity, Leptospira, Leptospirosis, Myeloperoxidase, Neutrophils
in
Virulence
volume
9
issue
1
pages
12 pages
publisher
Landes Bioscience
external identifiers
  • scopus:85053329060
ISSN
2150-5594
DOI
10.1080/21505594.2017.1407484
language
English
LU publication?
yes
id
c4f7cfa9-de10-4e10-b72a-0351731df72b
date added to LUP
2018-10-24 13:47:06
date last changed
2019-10-15 06:48:54
@article{c4f7cfa9-de10-4e10-b72a-0351731df72b,
  abstract     = {<p>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.</p>},
  author       = {Vieira, Monica L. and Teixeira, Aline F. and Pidde, Giselle and Ching, Ana T.C. and Tambourgi, Denise V. and Nascimento, Ana Lucia T.O. and Herwald, Heiko},
  issn         = {2150-5594},
  keyword      = {Host-pathogen interactions,Immune evasion,Innate immunity,Leptospira,Leptospirosis,Myeloperoxidase,Neutrophils},
  language     = {eng},
  number       = {1},
  pages        = {414--425},
  publisher    = {Landes Bioscience},
  series       = {Virulence},
  title        = {Leptospira interrogans outer membrane protein lipl21 is a potent inhibitor of neutrophil myeloperoxidase},
  url          = {http://dx.doi.org/10.1080/21505594.2017.1407484},
  volume       = {9},
  year         = {2018},
}