9.5 Strategies for the use of Gene Knockout Mice in the Investigation of Bacterial Pathogenesis and Immunology

Publisher Summary

The availability of mouse mutants that are generated by targeted gene disruption has provided microbiologists and immunologists with exciting tools to investigate bacterial virulence and immunity, and for the investigation of vaccines and how they mediate their protective effect. The functionality of immune effector cells depend upon an intact cytokine regulatory network, and when deletion part of this interactive network is lost, some host immune cell populations are in turn disrupted and this causes loss of populations of cells from the systemic or local immune system. The approach to using knockout mice in the investigation of bacterial infection has the following two important provisos: (1) the mouse is a good model of disease relevant to the human or animal infection being studied, and (2) the possibility of immune cell compensation for the loss of cytokine or receptor, and redundancy within the immune system is realized when interpreting the results of experimental investigations. There are a number of effects that gene knockouts can have on bacterial infections in mice. They can range from dramatic signs of infection leading to death when challenged with a dose of the infectious agent that would not cause apparent infection in normal mice, to no obvious effect on the ability of the mice to control infection. The chapter further explains the use of cytokine and cytokine receptor knockout mice in the study of murine salmonellosis.