MyD88-dependent induction of allergic Th2 responses to intranasal antigen

Damani A. Piggott*, Stephanie C. Eisenbarth, Lan Xu, Stephanie L. Constant, James W. Huleatt, Christina A. Herrick, Kim Bottomly

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

201 Scopus citations


MyD88 is a common Toll-like receptor (TLR) adaptor molecule found to be essential for induction of adaptive Th1 immunity. Conversely, innate control of adaptive Th2 immunity has been shown to occur in a MyD88-independent manner. In this study, we show that MyD88 is an essential innate component in the induction of TLR4-dependent Th2 responses to intranasal antigen; thus we demonstrate what we believe to be a novel role for MyD88 in pulmonary Th2 immunity. Induction of the MyD88-independent type I IFN response to LPS is defective in the pulmonary environment. Moreover, in the absence of MyD88, LPS-induced upregulation of costimulatory molecule expression on pulmonary DCs is defective, in contrast to what has been observed with bone marrow-derived DCs (BMDCs). Reconstitution of Th2 responses occurs upon adoptive pulmonary transfer of activated BMDCs to MyD88-deficient recipients. Furthermore, the dependence of Th2 responses on MyD88 is governed by the initial route of antigen exposure; this demonstrates what we believe are novel site-specific innate mechanisms for control of adaptive Th2 immunity.

Original languageEnglish (US)
Pages (from-to)459-467
Number of pages9
JournalJournal of Clinical Investigation
Issue number2
StatePublished - Feb 2005
Externally publishedYes

ASJC Scopus subject areas

  • Medicine(all)


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