The groundbreaking research of Stephan Rosshart (now in Erlangen) puts a question mark on several decades immunology and infection research carried out in inbred SPF lab mice: they are simply too clean to be useful as a model for human disease.
A new paper by Rosshart in TiM may serve as a primer into the field
Specifc pathogen-free mice have shaped modern immunology, but they exist in an ecological vacuum, far removed from the microbial realities that have shaped mammalian immunity. Recognizing microbial self and nonself as integral to the immune identity of the metaorganism reframes our understanding of tolerance, memory, and disease. Recent ndings indicate that microbial peptides play a direct role in thymic selection … This can occur either through the direct transport of commensal-derived antigens to the thymus … or indirectly via tonic IFN production that shapes the selection process.
see also “Mice and Men with Asthma“