Differential activation of dendritic cells by Toll-like receptor agonists isolated from the Gram-positive vaccine vector Streptococcus gordonii.

Abstract:

:The oral commensal bacterium Streptococcus gordonii has been gathering interest as a candidate live mucosal vaccine delivery vector. S. gordonii has been shown to be capable of activating antigen presenting immune cells in a manner which leads to their activation and maturation, yet the mechanism used by S. gordonii to do so is poorly understood. The aim of this work was to investigate the immunostimulatory components of S. gordonii in inducing murine dendritic cell (DC) activation and maturation. Lipoteichoic acid (LTA), lipoprotein (LP), peptidoglycan (PGN), and DNA were isolated from S. gordonii, and used to stimulate murine DC. Cytokine production and DC surface marker upregulation in response to the bacterial components was quantified by enzyme-linked immunosorbent assay and flow cytometry respectively. The results were contrasted against data obtained from DC derived from MyD88, TRIF [TIR(Toll/Interleukin-1 Receptor)-domain-containing adapter-inducing interferon-beta] or toll-like receptor-2 (TLR-2) knockout mice. The four S. gordonii bacterial components were found to differentially induce cytokine production and surface marker upregulation by murine DC. Activation of DC by both whole S. gordonii cells and the four bacterial components was abrogated in the absence of MyD88, but not in the absence of TRIF. LTA, LP and PGN, but not DNA and whole S. gordonii, required TLR-2 to induce a DC response. The results collectively indicate that S. gordonii activates DC predominantly through a MyD88-dependent and TRIF-independent pathway. This activation can be attributed to multiple immunostimulatory components present within S. gordonii bacterial cells.

journal_name

Scand J Immunol

authors

Mayer ML,Phillips CM,Townsend RA,Halperin SA,Lee SF

doi

10.1111/j.1365-3083.2009.02232.x

subject

Has Abstract

pub_date

2009-04-01 00:00:00

pages

351-6

issue

4

eissn

0300-9475

issn

1365-3083

pii

SJI2232

journal_volume

69

pub_type

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