Background: Streptococcus pyogenes (group A streptococcus (GAS)) causes a variety of diseases ranging from mild to severe infections. GAS express an arsenal of virulence factors, which impair the immune response resulting in successful establishment of infection. Dendritic cells (DCs) are innate immune sentinels specialized in antigen uptake and subsequent T cell priming. Interleukin (IL)-18, which is secreted by DCs, is regarded as a proinflammatory cytokine that facilitates mainly type 1 responses.
Methods: Human primary monocyte-derived (mo)DCs were used. DC maturation in response to infections with GAS 5448 and several mutant strains (Δemm1, Δslo, Δsls, 5448AP) was assessed via flow cytometry. In addition, multiple cytokines released by moDCs were measured.
Results: MoDCs readily matured in response to all infections by upregulating CD40 and MHCII molecules on the surface. Furthermore, expansion of CD83+ and CD86+ cells was noted. Infected moDCs secreted a broad range of cytokines. However, abrogated release of IL-8 and IL-18 was exclusively noted in response to 5448AP infections. As a proof-of-concept, human primary monocytes and monocyte-derived macrophages were also infected. Similarly, reduced IL-18 release was evident in infections with 5448AP.
Conclusions Our data demonstrate that the hyper-virulent 5448AP, which harbors covR/S mutations, interferes with IL-18 response in immune cells of myeloid lineage. Future experiments aim to decipher the mechanism of IL-18 suppression and its consequences for T cell priming.