Lactobacillus gasseri attenuates allergic airway inflammation through PPARγ activation in dendritic cells

Miao-Hsi Hsieh, Ren-Long Jan, Lawrence Shih-Hsin Wu, Pei-Chi Chen, Hui-Fang Kao, Wen-Shuo Kuo, Jiu-Yao Wang

Lactobacilli prevent the early development of allergic diseases in children and experimental asthma in mice. However, the detailed mechanism underlying this action remains unknown. We aimed to explore the activation pathway in the host by Lactobacillus and identify its immunomodulation mechanism in allergic asthma. Continuous administration of 10(7) cfu, but not 10(9) cfu, of L. gasseri for 4 weeks prevented Dermatophagoides pteronyssinus (Der p)-induced airway hypersensitivity and inflammation in a mouse model of allergic asthma. DNA microarray analysis of the mesenteric and lung draining lymph nodes revealed a significant decrease in inflammatory chemokines and increase in gene expression in carbohydrate and lipid metabolism, particularly of PPARγ, in 10(7) cfu L. gasseri-administered mice compared with untreated mice. Compared with WT mice, Der p-sensitized PPARγ(L/+) mice showed increased airway hyperresponsiveness to methacholine, inflammatory cell infiltration, and inflammatory cytokine secretion in bronchoalveolar fluid. Moreover, the protective effects of L. gasseri were lost in Der p-induced airway inflammation in PPARγ(L/+) mice, and L. gasseri-induced PPARγ activation in BMDCs inhibited the development of allergic airway inflammation in both PPARγ WT and PPARγ(L/+) mice. L. gasseri may act via a novel PPARγ activation pathway in DCs to alleviate allergen-induced airway inflammation in allergic asthma. L. gasseri prevents mite allergen (Der p)-induced airway inflammation. Prevention of airway inflammation occurs via activation of PPARγ in dendritic cells. L. gasseri administration does not reverse Der p-induced airway inflammation in PPARγ((+/-)) mice. L. gasseri-induced PPARγ activation inhibits development of airway inflammation in WT and PPARγ((+/-)) mice.