Inhibition of dendritic cell maturation by group A Streptococcus.

Abstract

Exposure to group A Streptococcus (GAS) has been shown to induce maturation of dendritic cells (DC). To identify bacterial determinants that modulate DC activation in response to GAS infection, we analyzed the induction of maturation in human monocyte-derived DC following exposure to GAS clinical isolates. Unexpectedly, only 6 of 24 GAS strains tested induced surface expression of major histocompatibility complex class II and costimulatory molecules CD80 and CD83 to levels consistent with DC maturation. Rather, the majority of the strains did not promote DC maturation, and many triggered DC apoptosis. GAS strains that failed to induce DC maturation were those that produced abundant hyaluronic acid (HA) capsular polysaccharide and/or large amounts of the cytotoxin streptolysin O (SLO). By use of isogenic mutants deficient in HA and/or SLO, we determined that GAS inhibits DC maturation through 2 distinct mechanisms: (1) inhibition of bacterial binding and/or phagocytosis by the HA capsule and (2) SLO-mediated induction of DC apoptosis by intracellular GAS. These results demonstrate that GAS virulence factors modulate maturation and survival of human DC, effects that are likely to have a critical impact on activation of innate and adaptive immune responses to this important human pathogen.