Format

Send to:

Choose Destination
See comment in PubMed Commons below
Infect Immun. 2009 Jun;77(6):2499-507. doi: 10.1128/IAI.01562-08. Epub 2009 Mar 30.

Campylobacter jejuni-induced activation of dendritic cells involves cooperative signaling through Toll-like receptor 4 (TLR4)-MyD88 and TLR4-TRIF axes.

Author information

  • 1Comparative Enteric Diseases Laboratory, National Food Safety and Toxicology Center, Michigan State University, East Lansing, MI 48824, USA.

Abstract

Campylobacter jejuni is an important cause of human enteritis and has been linked to the development of autoimmune diseases. Recently we showed that infection of murine dendritic cells (DCs) with C. jejuni resulted in DC activation and induction of Campylobacter-specific Th1-effector responses. Toll-like receptor (TLR) signaling through myeloid differentiation factor 88 (MyD88) and/or Toll-interleukin 1 (IL-1) receptor domain-containing adaptor-inducing beta interferon (IFN-beta) (TRIF) is critical in inducing immunity against pathogens. In this study, we investigated the role of TLR2, TLR4, MyD88, and TRIF signaling in C. jejuni-induced inflammatory activation of DCs. DC upregulation of major histocompatibility complex class II and costimulatory molecules after C. jejuni challenge was profoundly impaired by TLR2, TLR4, MyD88, and TRIF deficiencies. Similarly, C. jejuni-induced secretion of IL-12, IL-6, and tumor necrosis factor alpha was significantly inhibited in TLR2(-/-), TLR4(-/-), MyD88(-/-), and TRIF(-/-) DCs compared to that in wild-type DCs; however, the magnitude of inhibition was greater in MyD88(-/-), TRIF(-/-), and TLR4(-/-) DCs than in TLR2(-/-) DCs. Furthermore, C. jejuni induced interferon regulatory factor 3 phosphorylation and IFN-beta secretion by DCs in a TLR4-TRIF-dependent fashion, further demonstrating activation of this pathway by C. jejuni. Importantly, TLR2, TLR4, MyD88, and TRIF deficiencies all markedly impaired the Th1-priming ability of C. jejuni-infected DCs. Thus, our results show that cooperative signaling through the TLR4-MyD88 and TLR4-TRIF axes represents a novel mechanism mediating C. jejuni-induced inflammatory responses of DCs. To our knowledge, such a mechanism has not been demonstrated previously for an intact bacterium.

PMID:
19332531
[PubMed - indexed for MEDLINE]
PMCID:
PMC2687361
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for HighWire Icon for PubMed Central
    Loading ...
    Write to the Help Desk