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The secreted virulence factor Nadase of Group A Streptococcus inhibits P2X7 receptor-mediated release of IL-1β

Westerlund, Elsa LU ; Valfridsson, Christine LU ; Yi, Daisy X. and Persson, Jenny J. LU (2019) In Frontiers in Immunology 10(JUN).
Abstract

The common human pathogen Group A Streptococcus (GAS) causes superficial as well as invasive, life-threatening diseases. An increase in the occurrence of invasive GAS infection by strains of the M1 and M89 serotypes has been correlated with increased expression of the genetically and functionally linked virulence factors streptolysin O (SLO) and β-NAD+-glycohydrolase (NADase). NADase affects host cells differently depending on its location: its SLO-dependent translocation into the cytosol can lead to cell death through β-NAD+ depletion, while extracellularly located NADase inhibits IL-1β release downstream of Nlrp3 inflammasome activation. In this study, we use a macrophage infection model to investigate the NADase-dependent inhibition... (More)

The common human pathogen Group A Streptococcus (GAS) causes superficial as well as invasive, life-threatening diseases. An increase in the occurrence of invasive GAS infection by strains of the M1 and M89 serotypes has been correlated with increased expression of the genetically and functionally linked virulence factors streptolysin O (SLO) and β-NAD+-glycohydrolase (NADase). NADase affects host cells differently depending on its location: its SLO-dependent translocation into the cytosol can lead to cell death through β-NAD+ depletion, while extracellularly located NADase inhibits IL-1β release downstream of Nlrp3 inflammasome activation. In this study, we use a macrophage infection model to investigate the NADase-dependent inhibition of IL-1β release. We show that bacteria expressing a functional NADase evade P2X7 activation, while infection with a NADase-deficient GAS strain leads to a P2X7-mediated increase in IL-1β. Further, our data indicate that in the absence of NADase, IL-1β is released through both P2X7-dependent and -independent pathways, although the precise mechanisms of how this occur are still unclear. This study adds information about the mechanism by which NADase regulates inflammasome-dependent IL-1β release, which may in part explain why increased NADase expression correlates with bacterial virulence.

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author
; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Group A Streptococcus, IL-1β, Membrane permeabilization, NADase, P2X7
in
Frontiers in Immunology
volume
10
issue
JUN
article number
1385
publisher
Frontiers Media S. A.
external identifiers
  • scopus:85069179117
  • pmid:31275321
ISSN
1664-3224
DOI
10.3389/fimmu.2019.01385
project
On the effects of Streptococcal NAD+-glycohydrolase and Streptolysin O on macrophages
language
English
LU publication?
yes
id
2bcf0294-4c56-4525-9b11-a3d72167828b
date added to LUP
2019-07-26 15:34:49
date last changed
2024-06-11 22:24:29
@article{2bcf0294-4c56-4525-9b11-a3d72167828b,
  abstract     = {{<p>The common human pathogen Group A Streptococcus (GAS) causes superficial as well as invasive, life-threatening diseases. An increase in the occurrence of invasive GAS infection by strains of the M1 and M89 serotypes has been correlated with increased expression of the genetically and functionally linked virulence factors streptolysin O (SLO) and β-NAD+-glycohydrolase (NADase). NADase affects host cells differently depending on its location: its SLO-dependent translocation into the cytosol can lead to cell death through β-NAD+ depletion, while extracellularly located NADase inhibits IL-1β release downstream of Nlrp3 inflammasome activation. In this study, we use a macrophage infection model to investigate the NADase-dependent inhibition of IL-1β release. We show that bacteria expressing a functional NADase evade P2X7 activation, while infection with a NADase-deficient GAS strain leads to a P2X7-mediated increase in IL-1β. Further, our data indicate that in the absence of NADase, IL-1β is released through both P2X7-dependent and -independent pathways, although the precise mechanisms of how this occur are still unclear. This study adds information about the mechanism by which NADase regulates inflammasome-dependent IL-1β release, which may in part explain why increased NADase expression correlates with bacterial virulence.</p>}},
  author       = {{Westerlund, Elsa and Valfridsson, Christine and Yi, Daisy X. and Persson, Jenny J.}},
  issn         = {{1664-3224}},
  keywords     = {{Group A Streptococcus; IL-1β; Membrane permeabilization; NADase; P2X7}},
  language     = {{eng}},
  month        = {{06}},
  number       = {{JUN}},
  publisher    = {{Frontiers Media S. A.}},
  series       = {{Frontiers in Immunology}},
  title        = {{The secreted virulence factor Nadase of Group A Streptococcus inhibits P2X7 receptor-mediated release of IL-1β}},
  url          = {{http://dx.doi.org/10.3389/fimmu.2019.01385}},
  doi          = {{10.3389/fimmu.2019.01385}},
  volume       = {{10}},
  year         = {{2019}},
}