Pharmaceutical Sciences Faculty Publications

Title

Prostaglandin E2 is a Major Inhibitor of Dendritic Cell Maturation and Function in Ixodes Scapularis Saliva

Document Type

Article

Publication Date

8-1-2007

Journal Title

Journal of Immunology

ISSN

0022-1767

Volume

179

Issue

3

First Page

1497

Last Page

1505

DOI

10.4049/jimmunol.179.3.1497

PubMed ID

17641015

Abstract

Tick saliva is thought to contain a number of molecules that prevent host immune and inflammatory responses. In this study, the effects of Ixodes scapularis saliva on cytokine production by bone marrow-derived dendritic cells (DCs) from C57BL/6 mice stimulated by TLR-2, TLR-4, and TLR-9 ligands were studied. Saliva at remarkably diluted concentrations (<1/2000) promotes a dose-dependent inhibition of IL-12 and TNF-alpha production induced by all TLR ligands used. Using a combination of fractionation techniques (microcon filtration, molecular sieving, and reversed-phase chromatography), we unambiguously identified PGE(2) as the salivary inhibitor of IL-12 and TNF-alpha production by DCs. Moreover, we have found that I. scapularis saliva (dilution 1/200; approximately 10 nM PGE(2)) marginally inhibited LPS-induced CD40, but not CD80, CD86, or MHC class II expression. In addition, saliva significantly suppressed the ability of DCs to stimulate Ag-specific CD4(+) T cell proliferation and IL-2 production. Notably, the effect of saliva on DC maturation and function was reproduced by comparable concentrations of standard PGE(2). These findings indicate that PGE(2) accounts for most inhibition of DC function observed with saliva in vitro. The role of salivary PGE(2) in vector-host interaction and host immune modulation and inflammation in vivo is also discussed. This study is the first to identify molecularly a DC inhibitor from blood-sucking arthropods.

Keywords

Bone marrow cells, cell differentiation, cells, cultured, cytokines, dendritic cells, dinoprostone, growth inhibitors, inflammation mediators, ixodes, transgenic, saliva

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