Ramp-ing up allergies: Nramp1 (Slc11a1), macrophages and the hygiene hypothesis.

The ‘hygiene hypothesis’ suggests that a lack of infections favours the development of allergic disease. Mycobacteria and helminths are important in the hygiene hypothesis as infections caused by these agents generate regulatory mechanisms that can restore the immune balance. The hygiene hypothesis may be viewed as a complex multifactorial interaction between the environment and the genetic background of the individual, both of which contribute to the development of allergic disease. For instance, the Nramp1 gene (recently designated Slc11a1), which encodes bacterial resistance and determines the level of macrophage activation, affects treatment of allergic asthma with mycobacteria. Thus, Nramp1, and other innate immunity genes, might provide a link between the genetic background, the bacterial environment and the development of allergic diseases. It is likely that the macrophage has a crucial role in this link, connecting innate immunity with adaptive immunity in allergic disease.