MyD88-dependent induction of allergic Th2 responses to intranasal antigen
Damani A. Piggott, … , Christina A. Herrick, Kim Bottomly
Damani A. Piggott, … , Christina A. Herrick, Kim Bottomly
Published February 1, 2005
Citation Information: J Clin Invest. 2005;115(2):459-467. https://doi.org/10.1172/JCI22462.
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Article Immunology

MyD88-dependent induction of allergic Th2 responses to intranasal antigen

Abstract

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.

Authors

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

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Figure 1

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Th2 responses to intranasal protein antigen are MyD88 dependent. (A) BAL...
Th2 responses to intranasal protein antigen are MyD88 dependent. (A) BAL inflammatory cells of WT, MyD88-deficient, or TLR4d mice sensitized intranasally with OVA/LPS and WT mice sensitized with PBS. Exposed mice were then challenged 2 weeks later with inhaled OVA. Total bar height represents total BAL cell number, and error bars are based on total cell numbers. Stacked bars represent cell differential counts. n = 4. *P < 0.05, total BAL cell number from WT vs. MyD88-deficient and WT vs. TLR4d. One representative experiment of 4 is shown. (B) OVA-specific serum antibody responses by ELISA after challenge with OVA in WT, MyD88-deficient, and TLR4d mice sensitized as described in A. P < 0.05, WT vs. MyD88-deficient and WT vs. TLR4d, for IgE and IgG1 responses. (C) Cytokine production from lung draining lymph nodes after challenge with OVA in WT, MyD88-deficient, and TLR4d mice sensitized as described in A.