Lipopolysaccharide-enhanced, toll-like receptor 4-dependent T helper cell type 2 responses to inhaled antigen

Stephanie C. Eisenbarth, Damani Arnold Piggott, James W. Huleatt, Irene Visintin, Christina A. Herrick, Kim Bottomly

Research output: Contribution to journalArticle

Abstract

Allergic asthma is an inflammatory lung disease initiated and directed by T helper cells type 2 (Th2). The mechanism involved in generation of Th2 responses to inert inhaled antigens, however, is unknown. Epidemiological evidence suggests that exposure to lipopolysaccharide (LPS) or other microbial products can influence the development and severity of asthma. However, the mechanism by which LPS influences asthma pathogenesis remains undefined. Although it is known that signaling through Toll-like receptors (TLR) is required for adaptive T helper cell type 1 (Th1) responses, it is unclear if TLRs are needed for Th2 priming. Here, we report that low level inhaled LPS signaling through TLR4 is necessary to induce Th2 responses to inhaled antigens in a mouse model of allergic sensitization. The mechanism by which LPS signaling results in Th2 sensitization involves the activation of antigen-containing dendritic cells. In contrast to low levels, inhalation of high levels of LPS with antigen results in Th1 responses. These studies suggest that the level of LPS exposure can determine the type of inflammatory response generated and provide a potential mechanistic explanation of epidemiological data on endotoxin exposure and asthma prevalence.

Original languageEnglish (US)
Pages (from-to)1645-1651
Number of pages7
JournalJournal of Experimental Medicine
Volume196
Issue number12
DOIs
StatePublished - Dec 16 2002
Externally publishedYes

Fingerprint

Th2 Cells
Toll-Like Receptor 4
Lipopolysaccharides
Antigens
Asthma
Th1 Cells
Toll-Like Receptors
Endotoxins
Dendritic Cells
Inhalation
Lung Diseases

Keywords

  • Asthma
  • Dendritic cell
  • Lung
  • T cell
  • Toll-like receptor

ASJC Scopus subject areas

  • Immunology

Cite this

Lipopolysaccharide-enhanced, toll-like receptor 4-dependent T helper cell type 2 responses to inhaled antigen. / Eisenbarth, Stephanie C.; Piggott, Damani Arnold; Huleatt, James W.; Visintin, Irene; Herrick, Christina A.; Bottomly, Kim.

In: Journal of Experimental Medicine, Vol. 196, No. 12, 16.12.2002, p. 1645-1651.

Research output: Contribution to journalArticle

Eisenbarth, Stephanie C. ; Piggott, Damani Arnold ; Huleatt, James W. ; Visintin, Irene ; Herrick, Christina A. ; Bottomly, Kim. / Lipopolysaccharide-enhanced, toll-like receptor 4-dependent T helper cell type 2 responses to inhaled antigen. In: Journal of Experimental Medicine. 2002 ; Vol. 196, No. 12. pp. 1645-1651.
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