Pharyngitis caused by Streptococcus pyogenes (group A Streptococcus) is a common bacterial infection in humans, and a prerequisite to severe invasive diseases and sequelae. The ability of S. pyogenes to survive and establish infection likely involves its ability to modulate host immune defences; however the innate immune responses and signalling pathways that respond to S. pyogenes infection of epithelial tissues are not well understood. In this study we characterised the inflammatory responses of primary tonsil epithelial cells to infection with a laboratory-adapted M6 strain (JRS4) and a clinical isolate of the globally disseminated M1T1 clone (5448), the leading cause of pharyngitis and severe invasive S. pyogenes infections globally. We found JRS4 induces a strong IL-6 and IL-8 response during early infection of tonsil epithelial cells. In contrast 5448 induces a weak inflammatory response, suggesting 5448 is capable of dampening host innate immune function. This study suggests S. pyogenes serotypes can influence the scale and type of host immune responses generated during infection, and provides further insight into the intricate host-pathogen interactions that occur between S. pyogenes and the human immune system.