Contribution of Natural Killer Cells to the Pathogenesis of Septic Shock Induced byStreptococcus pyogenesin Mice

Abstract

Natural killer (NK) cells are critical components of the innate immune system and have been implicated in the pathogenesis of septic shock. In the present study, the relative contribution of NK cells to the development of Streptococcus pyogenes–induced septic shock was investigated in a mouse model of group A streptococcal infection that resembles the development of this condition in humans. C3H/HeN mice were depleted of NK cells by in vivo administration of anti–asialo ganglio-N-tetraosylceramide antibodies and then were examined for their response to infection with S. pyogenes NK cell–depleted mice exhibited increased survival times and slower development of disease during group A streptococcal infection than did nondepleted control mice. The augmented resistance to S. pyogenes observed in NK cell–depleted mice was associated with serum levels of proinflammatory cytokines such as interferon-γ, interleukin (IL)–12, and IL-6 during the early phase of infection that were much lower than those detected in nondepleted control mice. NK cell–deficient mutant mice were also more resistant to S. pyogenes than were the corresponding control mice. We conclude that NK cells, by amplifying the inflammatory response, significantly contribute to the progression of S. pyogenes–induced septic shock