Induction of alpha/beta interferon and dependent nitric oxide synthesis during Chlamydia trachomatis infection of McCoy cells in the absence of exogenous cytokine.
The propensity of two Chlamydia trachomatis strains (L2/434/Bu [biovar LGV] and E/DK20/ON [biovar trachoma]) to induce putative host defense responses upon infection of McCoy (mouse) cell cultures was examined. Both strains induced production of alpha/beta interferon and nitric oxide (NO) by McCoy cells. NO synthesis was mediated by the inducible isoform of NO synthase as indicated by the ability of cycloheximide or the arginine analog NG-monomethyl-L-arginine to abolish NO production; the extent of the response was dependent upon the dose of chlamydiae applied. Incubation of McCoy cells with chloramphenicol prior to infection reduced NO production by strain 434 but not by DK20, suggesting that initial chlamydial metabolism was essential to induction by the LGV strain. Antibody inhibition studies indicated that NO synthesis was dependent upon production of alpha/beta interferon and induction via lipopolysaccharide. Overall, our findings show that chlamydiae are capable of the induction of interferon and NO in murine fibroblasts in the absence of exogenous cytokines. However, the role of NO as an antichlamydial effector could not be clearly demonstrated since treatment with an arginine analog, while suppressing NO production, gave no consistent enhancement of infected cell numbers.
Devitt
A
A
Microbial Molecular Genetics and Cell Biology Group, School of Biological Sciences, University of Birmingham, United Kingdom. A.Devitt@bham.ac.uk
Lund
P A
PA
Morris
A G
AG
Pearce
J H
JH
D000818:Animals; D002478:Cells, Cultured; D002692:Chlamydia trachomatis / Q000502:physiology*; D006367:HeLa Cells; D016898:Interferon-alpha / Q000096:biosynthesis*; D016899:Interferon-beta / Q000096:biosynthesis*; D051379:Mice; D009569:Nitric Oxide / Q000096:biosynthesis*; D009573:Nitrites / Q000378:metabolism; D019323:omega-N-Methylarginine / Q000494:pharmacology
D016898:Interferon-alpha; D009573:Nitrites; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D016899:Interferon-beta