J Mol Med (Berl) 2018 01 14;96(1):39-51. Epub 2017 Oct 14.
Department of Pediatrics, Chi-Mei Medical Center, Liou-Yin, Tainan, Taiwan.
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 cfu, but not 10 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 cfu L. gasseri-administered mice compared with untreated mice. Compared with WT mice, Der p-sensitized PPARγ 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 mice, and L. gasseri-induced PPARγ activation in BMDCs inhibited the development of allergic airway inflammation in both PPARγ WT and PPARγ mice. L. gasseri may act via a novel PPARγ activation pathway in DCs to alleviate allergen-induced airway inflammation in allergic asthma.
Key Messages: 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.