Streptococcus pyogenes emm98.1 variants activate inflammatory caspases in human neutrophils

ABSTRACT

The human pathogen Streptococcus pyogenes (Group A Streptococcus, GAS) is responsible for invasive disease characterized by inflammation and tissue destruction. Inflammatory symptoms of invasive disease may be attributed to the neutrophil response during the early stages of infection. Here, the human neutrophil response to GAS was characterized in vitro using emm98.1 type covS mutant GAS strain NS88.2 (isolated from invasive infection) and avirulent variant NS88.2rep. NS88.2 was shown to resist phagocytic killing and proliferate in the presence of human neutrophils, where neutrophil antimicrobial defence through the production of reactive oxygen species was reduced compared with NS88.2rep. In the presence of NS88.2, neutrophil death was delayed compared with NS88.2rep. Infection with either GAS strain induced expression of inflammatory caspases-1 and -4 in neutrophils, with increased detection of activated inflammatory caspases in response to NS88.2rep compared with NS88.2. NS88.2 infection caused differential expression of cell-surface CD66b, CD16, and CD31, when compared to NS88.2rep. We conclude that the neutrophil response to NS88.2 promotes inflammation and may be a contributing factor to the severity of invasive GAS infections.

Abbreviations

CovRS, control of virulence regulatory system; GAS, Group A Streptococcus; PMN, polymorphonuclear leukocyte.

KEYWORDS:

• Neutrophils
• Streptococcus pyogenes
• inflammation
• cell death
• caspases

Acknowledgements

We thank all the generous participants for their sample donation and time. We thank the Molecular Horizons Fluorescence Analysis Facility at the University of Wollongong. This project was funded by the Illawarra Health and Medical Research Institute 2018 NHMRC Near Miss Scheme, awarded to MSS and RS. JW was a recipient of the Research Training Program Scholarship during this time.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Author contributions

JW: Conceptualization, methodology, formal analysis, investigation, writing – original draft, writing – review and editing, visualization. RS: Conceptualization, methodology, writing – review and editing, visualization, supervision, funding acquisition. MSS: Conceptualization, methodology, resources, writing – review and editing, visualization, supervision, funding acquisition. All authors adhere to ICMJE authorship guidelines and have approved the submitted version for publication.

Data availability statement

The raw data supporting the conclusions of this article are not freely available due to limits of ethics approval, however project requests can be made by contacting the corresponding author for access and amendments on a case-by-case basis.

Supplemental data

Supplemental data for this article can be accessed online at https://doi.org/10.1080/21505594.2023.2264090.

Additional information

Funding

The work was supported by the Illawarra Health and Medical Research Institute [2018 NHMRC Near Miss Scheme].