Indeed, a major recent study explicitly linked evolutionary pressure of helminth infection with autoimmune disease via adaptation of the FcγR genes [117]. It supports the hygiene hypothesis, which states that in the absence of chronic helminth infection, as seen in modern first-world populations, previously selected FcγR alleles respond differently to immune system challenges and therefore alter the susceptibility
to autoimmune disease [80]. It also points towards genetic and evolutionary investigation of complex structurally variable genomic regions that contain immune genes, of which there are many [118], as an approach to finding disease susceptibility alleles. Further, the ‘antibody theory’ to explain the hygiene hypothesis is readily testable in the H. p. bakeri model, and we therefore propose a number of experiments for future investigations: IgG purified from chronic primary infected animals is better at PI3K inhibitor interacting with low-affinity inhibitory receptors than
IgG purified from naïve or vaccinated individuals and thus will be more effective at protecting against autoimmune disease in mouse models. Different mouse strains will exhibit genetic variability of their FcγR and SIGLECs that predict many of the immunological phenotypes discussed above, and Chronic infection leads to B cells with selleck products modulated IgG–Fc glycosylation [119]. We also anticipate the discovery of H. p. bakeri glycosidases exquisitely specific for the sugars on IgG, as are known for bacteria
[120]. These may even lead to the development of new therapies for autoimmune disease as recently demonstrated for bacterial Acetophenone endoglycosidase S [121]. With the rapid growth of sequencing technologies, already well under way for H. p. bakeri, the genome of the parasite is likely to be fully known in the very near future, and this information should accelerate greatly the discovery of parasite genes and their products. As mentioned above, antibodies may also prove useful in identifying parasite products that interfere with host responses, although the mechanistic role of antibodies in this process first needs to be addressed. The factors regulating antibody production also need to be identified clearly. Previous findings that different mouse strains exhibit poor or strong immunity correlating with the speed and extent of specific antibody production [64, 15, 65] highlight genetics as a major determinant of the antibody-dependent protective immune responses in this system. Today various recombinant inbred mouse lines are available for use in quantitative trait loci (QTL) studies, and these could be exploited to build on the work that has already been pioneered in inbred mouse strains [122, 123] to provide ever-refined loci for genes involved in protective and other accompanying responses.