Localization of TLR2 and MyD88 to Chlamydia trachomatis inclusions. Evidence for signaling by intracellular TLR2 during infection with an obligate intracellular pathogen.
Chlamydia trachomatis is an obligate intracellular gram-negative pathogen and the etiologic agent of significant ocular and genital tract diseases. Chlamydiae primarily infect epithelial cells, and the inflammatory response of these cells to the infection directs both the innate and adaptive immune response. This study focused on determining the cellular immune receptors involved in the early events following infection with the L2 serovar of C. trachomatis. We found that dominant negative MyD88 inhibited interleukin-8 (IL-8) secretion during a productive infection with chlamydia. Furthermore, expression of Toll-like receptor (TLR)-2 was required for IL-8 secretion from infected cells, whereas the effect of TLR4/MD-2 expression was minimal. Cell activation was dependent on infection with live, replicating bacteria, because infection with UV-irradiated bacteria and treatment of infected cells with chloramphenicol, but not ampicillin, abrogated the induction of IL-8 secretion. Finally, we show that both TLR2 and MyD88 co-localize with the intracellular chlamydial inclusion, suggesting that TLR2 is actively engaged in signaling from this intracellular location. These data support the role of TLR2 in the host response to infection with C. trachomatis. Our data further demonstrate that TLR2 and the adaptor MyD88 are specifically recruited to the bacterial or inclusion membrane during a productive infection with chlamydia and provide the first evidence that intracellular TLR2 is responsible for signal transduction during infection with an intracellular bacterium.
O'Connell
Catherine M
CM
Department of Microbiology/Immunology, University of Arkansas for Medical Sciences, Little Rock, Arkansas 72205, USA.
Ionova
Irina A
IA
Quayle
Alison J
AJ
Visintin
Alberto
A
Ingalls
Robin R
RR
D048868:Adaptor Proteins, Signal Transducing / Q000502:physiology*; D002460:Cell Line; D002478:Cells, Cultured; D002584:Cervix Uteri / Q000166:cytology; D002692:Chlamydia trachomatis / Q000276:immunology* / Q000472:pathogenicity; D004847:Epithelial Cells / Q000382:microbiology / Q000502:physiology; D005260:Female; D006801:Humans; D007668:Kidney; D053594:Myeloid Differentiation Factor 88; D015398:Signal Transduction; D051195:Toll-Like Receptor 2 / Q000502:physiology*
D048868:Adaptor Proteins, Signal Transducing; C507779:MYD88 protein, human; D053594:Myeloid Differentiation Factor 88; C495342:TLR2 protein, human; D051195:Toll-Like Receptor 2