Rationale: Respiratory Mycoplasma pneumoniae (Mp) infection is involved in asthma pathobiology, but whether the established airway allergic inflammation compromises lung innate immunity and subsequently predisposes asthmatics to Mp infection remains unknown. Objectives: To test whether the established airway allergic inflammation compromises host innate immunity [e.g., Toll-like receptor 2 (TLR2)] to hinder the elimination of Mp from the lungs. Methods: We used mouse models of ovalbumin (OVA)-induced airway allergic inflammation with an ensuing Mp infection, and cultures of mouse primary lung dendritic cells (DCs) and bone marrow-derived DCs (BMDCs). Measurements and Main Results: Lung Mp clearance in allergic mice, TLR2 and IL-6 levels in lung cells including DCs as well as in cultured primary lung DCs and BMDCs were assessed. The established OVA-induced airway allergic inflammation, or the prominent Th2 cytokines IL- 4 and IL-13, inhibited TLR2 expression and IL-6 production in lung cells including lung DCs, and eventually led to impaired host defense against Mp. Studies in IL-6 knockout mice indicated that IL-6 directly promoted Mp clearance from the lungs. IL-4 and IL-13-induced suppression of TLR2 was mediated by inhibiting nuclear factor-B (NF-B) activation through signal transducer and activator of transcription 6 (STAT6) signaling pathway. Conclusions: The established OVA-induced airway allergic inflammation impairs TLR2 expression and host defense cytokine (e.g., IL-6) production, and subsequently delays lung bacterial clearance. This could offer novel therapeutic strategies to reinstate TLR2 activation by using TLR2 ligands and/or blocking IL-4 and IL-13 to ameliorate persisting respiratory bacterial infections in allergic lungs.