Chlamydia trachomatis induces expression of IFN-g-inducible protein 10 and IFN-b independent of TLR2 and TLR4, but largely dependent on MyD88Journal of Immunology
ORCiDDavid M. Ojcius: 0000-0003-1461-4495
AbstractIFN-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.
Citation InformationUma M. Nagarajan, David M. Ojcius, Lynn Stahl, Roger G. Rank, et al.. "Chlamydia trachomatis induces expression of IFN-g-inducible protein 10 and IFN-b independent of TLR2 and TLR4, but largely dependent on MyD88" Journal of Immunology Vol. 175 Iss. 1 (2005) p. 450 - 460 ISSN: 0022-1767
Available at: http://works.bepress.com/david-ojcius/65/