Gamma interferon-induced nitric oxide production reduces Chlamydia trachomatis infectivity in McCoy cells.
McCoy cells, murine-derived cells commonly used for propagation of chlamydiae, were found to be efficient producers of nitric oxide (NO) when primed with murine gamma interferon (IFN-gamma) and then exposed to the second signals provided by Escherichia coli lipopolysaccharide, human interleukin-1 alpha, murine tumor necrosis factor alpha, or Chlamydia trachomatis type H. Murine recombinant IFN-gamma over a range of 0 to 50 U/ml inhibited infectivity of C. trachomatis type H in a dose-dependent fashion in McCoy cells while simultaneously inducing NO production. Quantitation of infectious chlamydia progeny remaining in McCoy cells 48 or 72 h postinfection revealed that IFN-gamma-primed McCoy cells reduced chlamydial inclusion-forming units (expressed as units per milliliter) by 4 log10 units at higher IFN-gamma concentrations (50 U/ml) compared with control values. The magnitude of this antichlamydial effect was directly related to increased synthesis of NO, the production of which was IFN-gamma dose dependent. The antichlamydial effects of IFN-gamma were blocked in a dose-dependent manner by the addition of N-guanidino-monomethyl L-arginine (MLA), an inhibitor of nitric oxide synthesis. These results suggest that although IFN-gamma priming of McCoy cells is required for antichlamydial activity, nitric oxide is a necessary effector molecule involved in the mechanism(s) of IFN-gamma-induced inhibition of chlamydial proliferation in this murine cell line. The ability to block the potent antichlamydial effects of IFN-gamma by inhibition of a specific enzyme, nitric oxide synthase, may give insights into mechanisms by which IFN-gamma and perhaps other cytokines are able to control proliferation of chlamydiae and other intracellular pathogens.
Mayer
J
J
Division of Infectious Diseases, University of Utah School of Medicine, Salt Lake City 84132.
Woods
M L
ML
Vavrin
Z
Z
Hibbs
J B
JB
D000818:Animals; D001120:Arginine / Q000494:pharmacology; D002460:Cell Line; D002692:Chlamydia trachomatis / Q000187:drug effects* / Q000472:pathogenicity*; D007371:Interferon-gamma / Q000494:pharmacology*; D051379:Mice; D009569:Nitric Oxide / Q000378:metabolism*; D013997:Time Factors
D009569:Nitric Oxide; D007371:Interferon-gamma; D001120:Arginine