The role of innate immunity in the pathogenesis of asthma.
OBJECTIVE
The increase in prevalence of allergic diseases, in particular of asthma, poses great difficulties to healthcare institutions in industrialized countries. According to the hygiene hypothesis, a linkage exists between exposure towards microbes in early childhood and the development of allergies; however, the original view that stimulation of the host's immune system by microbes exclusively protects against the development of allergies and asthma has been challenged by recent studies, which are summarized in this review.


RESULTS
Recent studies in mice revealed that infection with a series of microbes in the context of allergen exposure enhances antigen sensitization. Furthermore, in studies using purified toll-like receptor ligands and live bacteria, innate immune activation via MyD88 has been shown to be a causative factor in sensitization. The view that innate immune activation, under circumstances yet to be elucidated, may be a causative factor for the development of allergies is backed by epidemiologic data showing a protective effect of genetic variants, which impair toll-like receptor signaling.


CONCLUSIONS
Recent studies in mice suggest that innate immune stimulation via microbes or their compounds, in a dose and time-dependent manner, can cause allergen sensitization, and this notion has lately been supported by epidemiologic data.
Schröder
Nicolas W J
NW
Institute for Neuropathology, Charité Medical Center, Berlin, Germany. nicolas.schroeder@charite.de
D000485:Allergens / Q000276:immunology; D000818:Animals; D001249:Asthma / Q000276:immunology* / Q000382:microbiology*; D003713:Dendritic Cells / Q000276:immunology; D004195:Disease Models, Animal; D006801:Humans; D007113:Immunity, Innate; D051379:Mice; D012141:Respiratory Tract Infections / Q000276:immunology / Q000382:microbiology; D051193:Toll-Like Receptors / Q000276:immunology
D000485:Allergens; D051193:Toll-Like Receptors