Abstract
Invasive infections due to group A Streptococcus (GAS) advance rapidly causing tissue degradation and unregulated inflammation. Neutrophils are the primary immune cells that respond to GAS. The neutrophil response to GAS was characterised in response to two M1T1 isolates; 5448 and animal passaged variant 5448AP. Co-incubation of neutrophils with 5448AP resulted in proliferation of GAS and lowered the production of reactive oxygen species when compared with 5448. Infection with both strains invoked neutrophil death, however apoptosis was reduced in response to 5448AP. Both strains induced neutrophil caspase-1 and caspase-4 expression in vitro, with inflammatory caspase activation detected in vitro and in vivo. GAS infections involving strains such as 5448AP that promote an inflammatory neutrophil phenotype may contribute to increased inflammation yet ineffective bacterial eradication, contributing to the severity of invasive GAS infections.
Highlights
Invasive infections due to the obligate human pathogen Streptococcus pyogenes are characterised by unregulated inflammation and high mortality (Davies et al, 1996; Svensson et al, 2000; O’Grady et al, 2007; O’Loughlin et al, 2007; Lamagni et al, 2008; Nelson et al, 2016)
Neutrophil phagocytic ability is a predominant and wellestablished mechanism of immune defence. Both group A Streptococcus (GAS) strains 5448 and 5448AP rapidly associated with human neutrophils, with near maximal association observed within 30 min (Figures 1A and S1A–C)
We describe an inflammatory neutrophil phenotype, as evidenced by increased caspase-1 and caspase-4 expression and inflammatory caspase activation in vitro and in vivo, that may promote inflammation and exacerbate GAS disease
Summary
Invasive infections due to the obligate human pathogen Streptococcus pyogenes (group A Streptococcus; GAS) are characterised by unregulated inflammation and high mortality (Davies et al, 1996; Svensson et al, 2000; O’Grady et al, 2007; O’Loughlin et al, 2007; Lamagni et al, 2008; Nelson et al, 2016). Due to these characteristics, 5448AP can be used as a model strain to explore the host response to invasive GAS infection
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