MyD88 dependent induction of Th2 responses in a mouse model of asthma

• Published in: Journal of allergy and clinical immunology 2004-02, Vol.113 (2), p.S176-S176
• Main Author: Piggott, D.A.
• Format: Article
• Language: English
• ISSN: 0091-6749; 1097-6825
• DOI: 10.1016/j.jaci.2004.01.069

CD4+ Th2 cells have been implicated in the pathology of allergic and asthmatic responses. Initiation of adaptive Th2 responses requires innate instruction. Although a role for the common innate Toll-like receptor (TLR) adaptor molecule MyD88 has been found for Th1 induction, the mechanism for generation of Th2 responses is unclear. Our recent studies demonstrate that Th2 responses to aeroallergens are induced at low LPS dose and Th1 responses are induced at high LPS dose in a CD40 dependent manner. Given that LPS signaling through TLR4 engages both MyD88 dependent and independent pathways, we sought to determine the role of MyD88 in the induction of pulmonary Th2 responses. Mice were subject to intranasal administration of ovalbumin protein (OVA) concomitant with LPS followed by an intranasal OVA challenge course. The marked eosinophilia, mucus production, IgE, and Th2 cytokines induced in wild type mice was significantly impaired in both TLR4 deficient and MyD88 −/− mice. Reconstitution of Th2 responses was observed in MyD88 −/− mice by sensitization with OVA together with either TNFα or alum. Increases in MHC Class II and B7.2 on pulmonary DC in WT mice in response to LPS were not observed in either TLR4 deficient or MyD88 −/− mice. Thus, microbial signaling through MyD88 is a critical factor in the induction of allergic Th2 responses.