Title

Dose-Dependent Immunomodulating Effects of Endotoxin in Allergic Airway Inflammation

Document Type

Article

Publication Date

4-1-2017

Publication Title

Innate Immunity

DOI

10.1177/1753425917690443

ISSN

1753-4267

Abstract

How very high exposure levels to endotoxin in a farming environment provide protection against respiratory allergic symptoms and low-to-moderate levels of endotoxin in urban homes promote allergic response is unclear. Dose-specific bacterial endotoxin or LPS-induced tolerance mechanisms can affect lung inflammations, coupled with the Th2 immune responses. Here, we explored the effects of intranasal exposure of LPS at two different doses (based on occupational exposures during handling of agricultural wastes) in OVA-sensitized allergic wild type (WT) and TLR4-KO mice, particularly, with respect to Th2 cytokines and Tregs level. Low-dose LPS (100 ng) exposure prohibited airway tolerance and failed to generate T-cell-dependent protection against lung inflammations in allergic mice. Furthermore, low Tregs at the inflammatory site and induced Th2 cytokines, as well as IL-6 and IL-25, suggested that low-dose LPS might be associated with the suppression of tolerance mechanisms. In contrast, high-dose LPS (20 µg) favored the suppression of Th2 cytokines, IL-6 and IL-25, but failed to induce Th1 cytokines (e.g. IFN-γ). Our results suggest that low-dose LPS can enhance airway allergic inflammation through failing of antigen-dependent immune regulatory homeostasis. The exposure levels of LPS can determine the generation of inflammatory responses in airway allergy.

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