Inhibition of TH2 responses by a secreted component of a common farm bacterium

Abstract

Abstract The rise in incidence of asthma and allergic diseases over the past half century has led to the development of the hygiene hypothesis, which posits that lack of exposure to environmental microbes during childhood leads to inappropriate immune responses to innocuous antigens. Evidence for the hygiene hypothesis is particularly compelling in studies of rural farm children, where infants that live on farms had reduced prevalence of asthma at school age, as compared to their non-farming counterparts. In particular, the presence of exopolysaccharide (EPS) in farm dust independently predicted lower rates of asthma diagnosis. The purpose of this study is to investigate the protective effects of EPS from a common farm microorganism, the hay bacillus B. subtilis, in limiting TH2-type inflammation in a mouse model of asthma. Treatment of house dust mite (HDM)-sensitized mice with EPS was sufficient to block eosinophilia and TH2 accumulation in the lungs, without affecting accumulation of other TH subsets. These effects were dependent on TLR4, the putative receptor for EPS, as EPS no longer protected against eosinophilia and TH2 infiltration in Tlr4−\− mice. Additionally, lung-derived dendritic cells exposed to EPS and HDM in vivo were phenotypically distinct from dendritic cells recovered from mice treated with HDM alone. These data support a protective role for EPS in the inhibition of allergic asthma, potentially by affecting TLR4-dependent dendritic cell priming of TH2 responses.