TLR2 Favors Allergic Airway Inflammation Through JNK Signaling Pathway with Activation of Autophagy

Background: Numerous studies indicate that TLR2 activation led to contradictory effects in asthma. In addition, the occurance of autophagy such an innate immune response in asthma pathogenesis is still incompletely understood. This study investigated the role of TLR2 and the underlying mechanisms in allergic airway inflammation (AAI) and autophagy activation. Methods: Wild-type (WT) and TLR2 knockout (TLR2-/-) mice were subjected to an ovalbumin (OVA)-immunized and airway-challenged model to investigate the role of TLR2 in AAI and autophagy activation. SP600125, a specific JNK inhibitor, was administered in mice to study its effects on AAI and autophagy activation. Findings: Our study showed that the expression of TLR2 was increased concomitantly with airway inflammation upon OVA challenge, and TLR2 deficiency was associated with a dramatical decrease in serum OVA-specific IgE, pulmonary inflammatory cells infiltration, goblet cell metaplasia and bronchoalveolar lavage fluid (BALF) inflammatory cytokine production. Meanwhile, the expression of inflammatory proteins in lung tissues, autophagy activation were induced in OVA-challenge mice, while such inductions were significantly weakened by TLR2 deficiency. Moreover, inhibition of JNK by SP600125 also down-regulated airway inflammation and autophagy activation in OVA-challenged WT mice. Interestingly, treating TLR2-/- mice with SP600125 upon OVA challenge showed similar pulmonary inflammation manifestations, lung inflammatory proteins expression as well as autophagy activation compared to that in vehicle-treated TLR2-/- mice. Interpretation: TLR2 might contribute to the maintenance of AAI through JNK signaling pathway accompanying with autophagy activation. These findings may provide a novel signal target for prevention of AAI. Funding Statement: This study was supported by the National Natural Science Foundation of China (NO. 81170030, 81270082) and Natural Science Foundation of Anhui Province (NO. 1908085QH311). Declaration of Interests: The authors declare no conflicts of interest. Ethics Approval Statement: All procedures were approved by the Animal Care and Use Committee of University of Science and Technology of China.