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

Research output: Contribution to journalArticle


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.


External organisations
  • University of California, Berkeley
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Immunology
  • Microbiology in the medical area


  • Group A Streptococcus, IL-1β, Membrane permeabilization, NADase, P2X7
Original languageEnglish
Article number1385
JournalFrontiers in Immunology
Issue numberJUN
Publication statusPublished - 2019 Jun 18
Publication categoryResearch

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