Pathogenic bacteria and host defense system have been evolved by their offense and defense. In vivo research is crucial for elucidation of interactions between them. I have investigated their offence and defense by various standpoints using mouse models of Listeria monocytogenes and Staphylococcus aureus infections. Herein, the results of my research including the roles of endogenous cytokines in host defense, the attenuation of host defense mechanism in obesity and diabetes, the development of vaccines against S. aureus infection by staphylococcal enterotoxin (SE) family molecules, and the emesis-inducing mechanism of SEA are described.