Group A Streptococcus Infection of the Nasopharynx Requires Proinflammatory Signaling Through the Interleukin-1 Receptor

• DOI: 10.1101/2020.06.12.149526
• Publication Date: 2020-06-14T23:25:12Z
• Authors: Doris L. LaRock; Raedeen Russell; Anders F. Johnson; Shyra Wilde; Christopher N. La...
• Keywords: Proinflammatory cytokine; Streptococcus Pyogenes; Respiratory tract

ABSTRACT Group A Streptococcus (GAS) is the etiologic agent of numerous high morbidity and mortality diseases which commonly have a highly proinflammatory pathology. One factor contributing to this inflammation GAS protease SpeB, directly activates cytokine interleukin-1β (IL-1β), independent canonical inflammasome pathway. IL-1β drives neutrophil activation recruitment that limits bacterial growth invasion during invasive skin soft tissue infections like necrotizing fasciitis. also causes pharyngitis (strep throat), upper respiratory tract its primary nidus for transmission. Since fitness selection species likely primarily site, we examined process in murine nasopharynx. SpeB still activated IL-1β, was required migration, but instead increased replication. Inhibiting or depleting neutrophils, both promote infection, prevented infection Prior antibiotic exposure nasopharynx, antibiotics were sufficient reverse attenuation previously observed when not present drive inflammation. Therefore, same fundamental mechanism has opposing effects on virulence at different body sites. Invasive disease may be limited part due specific adaptations inducing host are beneficial pharyngitis. IMPORTANCE Our previous reports showed restricts infection. The site colonization host-pathogen interactions largely unknown. We provide first evidence IL-1β-mediated promotes This provides experimental notable strep throat, presents with significant swelling, pain, influx, an ineffectual immune response, rather GAS-directed remodeling niche pathogenic benefit.