Chapter 9 - Analysis of Genetic Susceptibility to Infection in Mice

Abstract

This chapter presents a genetic analysis of infection in mice. Exposure of inbred mice to infectious pathogens results in the activation of a broad network of innate (non-adaptive) and immune (adaptive) responses. The innate system acts as the first component of host resistance by controlling pathogen growth during the acute phase of infection. A basic difference between the innate and immune systems is the recognition of pathogen-associated molecular patterns (PAMPs) by the innate host defense system. PAMPs are invariant ligands on foreign invaders and include lipopolysaccharides (LPS), yeast mannans, and double-stranded RNA. The host receptors, which recognize PAMPs include C-type lectins on natural killer (NK) cells and scavenger receptors on macrophages. There are several immunological models, which have been used to investigate the role of adaptive immune function on resistance to infection in mice. The athymic, hairless nude mouse has been a long-standing tool to analyze the T-cell arm of the cellular immune response to several infections, including BCG. The SCID (severe combined immune deficiency)mouse model has been used recently to study human immune responses to influenza virus. Among the first models to study the effect of modifier genes was the creation of cystic fibrosis transmembrane conductance regulator (CFTR)-deficient mice on different inbred backgrounds. The results showed the existence of major modifier genes, which clearly changed the disease severity of the cystic fibrosis phenotype.