Group A Streptococcus emm3 strains induce early macrophage cell death

• Published in: Pathogens and disease Vol. 74; no. 2; p. ftv124
• Main Authors: Dinis, Márcia, Plainvert, Céline, Longo, Magalie, Guignot, Julie, Gabriel, Christelle, Poyart, Claire, Fouet, Agnès
• Format: Journal Article
• Language: English
• Published: United States Oxford University Press 01.03.2016
• Subjects: Animals; Caspase 3 - metabolism; Cell Death - immunology; Cytokines - metabolism; Disease Models, Animal; Female; Genetic Variation; Genotype; Inflammation Mediators - metabolism; Macrophages - immunology; Macrophages - metabolism; Macrophages - microbiology; Mice; Phagocytosis - immunology; Streptococcal Infections - immunology; Streptococcal Infections - metabolism; Streptococcal Infections - microbiology; Streptococcus pyogenes - classification; Streptococcus pyogenes - isolation & purification; Streptococcus pyogenes - pathogenicity; Streptococcus pyogenes - physiology; Virulence; cytokine; macrophages; virulence; cell death; genotype; Streptococcus pyogenes; emm genotype
• ISSN: 2049-632X; 2049-632X
• DOI: 10.1093/femspd/ftv124

Group A Streptococcus (GAS) infections present high morbidity and mortality rates and consequently remain a significant health problem. The emm3 isolates induce more severe pathologies than all others. In this study, we tested, on a collection of invasive and non-invasive emm3 clinical isolates, whether in that genotype the invasive status of the strains affects the innate immune response. We show that phagocytosis is dependent on the invasiveness of the isolates. Interestingly, all emm3 isolates compromise macrophage integrity, already noticeable 1 h after infection. Inflammatory modulators (IL-6, TNF-α and IFN-β) are nevertheless detected during at least 6 h post-infection. This is a likely consequence of the macrophages not being all infected. The efficient and rapid induction of macrophage death could explain the virulence of the emm3 strains. Group A Streptococcus emm3 isolates cause severe pathologies in part by inducing early macrophage cell death and thus compromising their integrity. Graphical Abstract Figure. Group A Streptococcus emm3 isolates cause severe pathologies in part by inducing early macrophage cell death and thus compromising their integrity.