Toll-like receptor 2 down-regulation in established mouse allergic lungs contributes to decreased mycoplasma clearance.
RATIONALE: Respiratory Mycoplasma pneumoniae (Mp) infection is involved in asthma pathobiology, but whether the established allergic airway inflammation compromises lung innate immunity and subsequently predisposes patients with asthma to Mp infection remains unknown. Objectives: To test whether the established allergic airway 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 allergic airway inflammation with an ensuing Mp infection, and cultures of mouse primary lung dendritic cells (DCs) and bone marrow-derived DCs. MEASUREMENTS AND MAIN RESULTS: Lung Mp clearance in allergic mice and TLR2 and IL-6 levels in lung cells, including DCs as well as cultured primary lung DCs and bone marrow-derived DCs, were assessed. The established OVA-induced allergic airway 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-kappaB activation through signal transducer and activator of transcription 6 (STAT6) signaling pathway. CONCLUSIONS: The established OVA-induced allergic airway 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.[1]References
- Toll-like receptor 2 down-regulation in established mouse allergic lungs contributes to decreased mycoplasma clearance. Wu, Q., Martin, R.J., Lafasto, S., Efaw, B.J., Rino, J.G., Harbeck, R.J., Chu, H.W. Am. J. Respir. Crit. Care Med. (2008) [Pubmed]
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