Galleria mellonella proteomic response to infection with Streptococcus pyogenes

Galleria mellonella is considered a suitable alternative infection model for studying microbial infections. Unlike conventional animal models, invertebrate models are readily available and not restricted by ethical concerns. Husbandry, maintenance, and handling of G. mellonella larvae are relatively simple. Furthermore, the insect innate immune system, consisting of a humoral and a cellular branch, shares similarities with the mammalian immune system. Streptococcus pyogenes is a strictly human pathogen responsible for a range of clinical manifestations, from superficial uncomplicated infections to severe invasive diseases. Over the past decade, S. pyogenes infection, serotype-specific virulence, and antimicrobial treatment have been studied using G. mellonella larvae. To further validate the G. mellonella infection model, this study investigated the S. pyogenes-specific response of the larvae using a proteomics approach. Infected larvae responded by upregulation of recognition molecules, antimicrobial peptides, and general stress pathways and by activation of the phenol oxidase pathway. In addition, factors known to be involved in the inflammatory response in humans were upregulated, including 15-hydroxyprostaglandin dehydrogenase, macrophage migration inhibitory factor, and nucleobindin-2. In particular, the levels of C-type lectin receptors and C4b-binding protein alpha were elevated. In humans and mice, these proteins are known to interact directly with S. pyogenes during the course of infection. Taken together, these results support the suitability of the G. mellonella model for studying S. pyogenes infection to reduce the use of vertebrate model organisms.