A model of invasive type of Streptococcus pyogenes infection after intranasal superinfection in influenza A virus-infected mice

Abstract

Streptococcus pyogenes (group A streptococcus; GAS) causes diseases ranging from benign to severe infections including acute respiratory distress syndrome, necrotizing faciitis, toxic shock-like syndrome. Apparent worldwide resurgence of invasive GAS infections in the last two decades remains unexplained. Currently, animal models in which toxic shock-like syndrome or necrotizing fasciitis is induced following GAS infection are not well developed. We demonstrate here that infection with a nonlethal dose of influenza A virus (IAV) before intranasal infection with a nonlethal dose of GAS organisms led to a death rate of more than 90% in mice, of which 10% showed necrotizing fasciitis. Infection of alveolar epithelial cells by the IAV resulted in viral hemagglutinin expression on the cell surface and promoted internalization of GAS. However, treatment with monoclonal antibodies to hemagglutinin markedly decreased this internalization. Our results indicate that prior infection with IAV induces a lethal synergism, resulting in the induction of invasive GAS infections in mice. In addition, immunization with formalin-inactivated IAV vaccine subcutaneously or IAV vaccine and cholera toxin intranasally protected mice from death by lethal IAV-GAS superinfection, suggesting that the vaccination may be useful in the prevention of lethal IAV-GAS infections. © 2004, Elsevier Inc. All rights reserved.