Title

Chlamydia trachomatis induces expression of IFN-g-inducible protein 10 and IFN-b independent of TLR2 and TLR4, but largely dependent on MyD88

ORCiD

David M. Ojcius: 0000-0003-1461-4495

Document Type

Article

Publication Title

Journal of Immunology

ISSN

0022-1767

Volume

175

Issue

1

DOI

10.4049/jimmunol.175.1.45

First Page

450

Last Page

460

Publication Date

7-1-2005

Abstract

IFN-γ-inducible protein 10 (IP-10) is a chemokine important in the attraction of T cells, which are essential for resolution of chlamydial genital tract infection. During infections with Gram-negative bacteria, the IP-10 response mediated through type I IFNs usually occurs as a result of TLR4 stimulation by bacterial LPS. However, we found that levels of IP-10 in genital tract secretions of Chlamydia trachomatis-infected female wild-type mice were similar to those of infected TLR2- and TLR4-deficient mice but significantly greater than those of infected MyD88-deficient mice. We investigated the mechanism of IP-10 and IFN-β induction during chlamydial infection using mouse macrophages and fibroblasts infected ex vivo. The induction of IP-10 and IFN-β was unchanged in Chlamydia-infected TLR2- and TLR4-deficient cells compared with wild-type cells. However, infection of MyD88-deficient cells resulted in significantly decreased responses. These results suggest a role for MyD88-dependent pathways in induction of IP-10 and IFN-β during chlamydial infection. Furthermore, treatment of infected macrophages with an endosomal maturation inhibitor significantly reduced chlamydial-induced IFN-β. Because endosomal maturation is required for MyD88-dependent intracellular pathogen recognition receptors to function, our data suggest a role for the intracellular pathogen recognition receptor(s) in induction of IFN-β and IP-10 during chlamydial infection. Furthermore, the intracellular pathways that lead to chlamydial-induced IFN-β function through TANK-binding kinase mediated phosphorylation and nuclear translocation of IFN regulatory factor-3.