Toll-like receptor 2 mediates Acanthamoeba-induced allergic airway inflammatory response in mice

Author summaryTLRs can recognize and bind to several PAMPs and trigger a series of signal transductions, ultimately leading to the release of inflammatory mediators, initiating the innate immune response, removing the invasive pathogenic microorganisms, and playing an important role in innate immune defense. According to many recent studies, TLR2 plays an important role in allergic diseases, such as asthma; however, its mechanism has not been fully revealed. Here, we demonstrated the interaction between the KA/E2 infection and TLR2 in vivo and in vitro. Although our findings provide invaluable insights into the mechanisms of the interaction between parasites and host, the mechanisms whereby KA/E2 infection induces allergic airway inflammation in the host should be clarified via further research. Overall, in this study, mice with TLR2 gene knockout were used as the study objects and KA/E2 trophozoites were induced as an allergen to establish the asthmatic mouse model. The role of TLR2 in the asthmatic mouse model and its possible mechanism of action were observed, thereby providing new insights into the pathogenesis of asthma and identifying new possible targets for asthma prevention and treatment. BackgroundRepeated intranasal exposure to Acanthamoeba has been revealed to induce allergic airway inflammatory responses in mice. Based on the role of toll-like receptors (TLRs) in the pathogenesis of allergic asthma, TLRs form a link between innate and adaptive immune responses, and play an important role in the activation of various cells in the innate immune system. Methodology/principal findingsTo determine the TLRs that are related to these immune responses, we assessed the expression levels of inflammation-related genes in mouse lung epithelial (MLE)-12 cells treated with excretory-secretory proteins (ES-P) of the Acanthamoeba strain (KA/E2) with or without the TLR antagonists. The expression levels of inflammation-related genes, such as eotaxin, TARC, macrophage-derived chemokine (MDC), and TSLP, in the TLR2 and TLR9 antagonist treatment groups were decreased, compared to those in the ES-P alone or other TLR antagonist treatment groups. In particular, a greater decrease in the relevant gene expression levels was found in the TLR2 antagonist treatment group than in the TLR9 antagonist treatment group. Allergic airway inflammation was evaluated in the wild-type (WT) and TLR2 knockout (KO) groups following KA/E2 exposure. Based on the results, allergic airway inflammatory responses (airway resistance value, inflammatory cell infiltration, Th2-related cytokine expression, mucin production, and metaplasia of lung epithelial cells and goblet cells) by KA/E2 were reduced in the TLR2 KO groups. In addition, TLR2 knockout BMDCs displayed lower activation of surface markers owing to ES-P stimulation than normal BMDCs, and KA/E2 ES-P-treated TLR2-depleted BMDCs produced fewer Th2 cytokine-expressing cells from naive T cells than WT BMDCs. When ES-P was administered after primary lung cells were obtained from WT and TLR2 KO mice, the expression levels of inflammation-related genes were found to be significantly decreased in TLR2 KO cells compared to those in WT cells. ConclusionsThese results suggest that TLR2 is involved in lung inflammatory response activation in KA/E2 intranasal infection, especially in airway tissue.