Induction of interferon-stimulated genes by Chlamydia pneumoniae in fibroblasts is mediated by intracellular nucleotide-sensing receptors.
BACKGROUND
Recognition of microorganisms by the innate immune system is mediated by pattern recognition receptors, including Toll-like receptors and cytoplasmic RIG-I-like receptors. Chlamydia, which include several human pathogenic species, are obligate intracellular gram-negative bacteria that replicate in cytoplasmic vacuoles. The infection triggers a host response contributing to both bacterial clearance and tissue damage. For instance, type I interferons (IFN)s have been demonstrated to exacerbate the course of Chlamydial lung infections in mice.


RESULTS
Here we show that Chlamydia pneumoniae induces expression of IFN-stimulated genes (ISG)s dependent on recognition by nucleotide-sensing Toll-like receptors and RIG-I-like receptors, localized in endosomes and the cytoplasm, respectively. The ISG response was induced with a delayed kinetics, compared to virus infections, and was dependent on bacterial replication and the bacterial type III secretion system (T3SS).


CONCLUSIONS
Activation of the IFN response during C. pneumoniae infection is mediated by intracellular nucleotide-sensing PRRs, which operate through a mechanism dependent on the bacterial T3SS. Strategies to inhibit the chlamydial T3SS may be used to limit the detrimental effects of the type I IFN system in the host response to Chlamydia infection.
Chiliveru
Srikanth
S
Department of Medical Microbiology and Immunology, Aarhus University, Aarhus, Denmark.
Birkelund
Svend
S
Paludan
Søren R
SR
D000818:Animals; D001426:Bacterial Proteins / Q000378:metabolism; D002478:Cells, Cultured; D023521:Chlamydophila Infections / Q000276:immunology; D016993:Chlamydophila pneumoniae / Q000276:immunology*; D005347:Fibroblasts / Q000382:microbiology*; D005796:Genes / Q000276:immunology; D054884:Host-Pathogen Interactions / Q000276:immunology; D007113:Immunity, Innate; D007372:Interferons / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009711:Nucleotides / Q000378:metabolism; D051192:Receptors, Pattern Recognition / Q000276:immunology*; D051193:Toll-Like Receptors; D015533:Transcriptional Activation / Q000276:immunology*
D001426:Bacterial Proteins; D009711:Nucleotides; D051192:Receptors, Pattern Recognition; D051193:Toll-Like Receptors; D007372:Interferons
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