Inhibition of Chlamydia pneumoniae replication in HEp-2 cells by interferon-gamma: role of tryptophan catabolism.
Interferon-gamma (IFN-gamma) induces tryptophan catabolism in HEp-2 cells, possibly via stimulation of host cell indoleamine-2,3-dioxygenase activity, in a dose-dependent (12.5-1600 U/mL) fashion after 24 h, resulting in a 99% conversion to its metabolites at 1600 U/mL. Replication of Chlamydia pneumoniae isolates A-03 and BAL-16 was inhibited in HEp-2 cells following treatment with 50 and 100 U/mL IFN-gamma, respectively; however, addition of excess L-tryptophan (200 microg/mL) to monolayers infected with C. pneumoniae resulted in unrestricted growth of both isolates up to 1600 U/mL IFN-gamma. C. pneumoniae could be recovered from IFN-gamma-treated monolayers, indicating the potential for this bacterium to undergo an altered life cycle, in vitro, analogous to that described in detail for Chlamydia trachomatis. The ability of C. pneumoniae to persist in host tissue despite an immunologic response would be an important attribute in order to cause or exacerbate chronic infections.
Mehta
S J
SJ
Department of Medicine, University of Louisville School of Medicine, Kentucky 40292, USA.
Miller
R D
RD
Ramirez
J A
JA
Summersgill
J T
JT
D000818:Animals; D002294:Carcinoma, Squamous Cell; D016993:Chlamydophila pneumoniae / Q000187:drug effects / Q000254:growth & development*; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology*; D007700:Kinetics; D008018:Life Cycle Stages; D013997:Time Factors; D014364:Tryptophan / Q000378:metabolism* / Q000494:pharmacology; D014366:Tryptophan Oxygenase / Q000378:metabolism; D014407:Tumor Cells, Cultured
D007371:Interferon-gamma; D014364:Tryptophan; D014366:Tryptophan Oxygenase