Inhibition of intracellular multiplication of human strains of Chlamydia trachomatis by nitric oxide.
It was previously shown that murine T cell clones could inhibit the intracellular growth of the mouse strain of Chlamydia trachomatis by cytokine-mediated induction of the inducible nitric oxide synthase (iNOS) system in epithelial cells, an effect enhanced by direct epithelial-T cell interaction via specific adhesion molecules. These findings and other recent reports showing that human mucosal epithelial cells secrete nitric oxide (NO) via iNOS expression would suggest that mucosal epithelial-derived NO may be involved in mucosal defense against Chlamydia and other pathogens that infect epithelial cells. As an initial approach to investigating whether NO contributes to chlamydial control in humans, the present studies evaluated the susceptibility of human isolates of C. trachomatis to NO delivered by chemical donors or via induction of the epithelial iNOS system by a cytokine-secreting T cell clone. It was found that a chlamydial-specific, cytokine-secreting, murine T lymphocyte clone (clone 2.14-0) could inhibit the intraepithelial growth of human strains of Chlamydia trachomatis (serovar E and H, and Lymphogranuloma venerum type L2) via the iNOS pathway when the clone was co-cultured with chlamydial-infected epithelial cells. Furthermore, treatment of infected epithelial cells with 50 microM of the NO donor, S-nitroso-L-glutathione, resulted in significant inhibition (approximately 70%) of chlamydial multiplication, while the NO scavenger, myoglobin plus ascorbate, could reverse the effect, demonstrating that NO could directly inhibit human strains of Chlamydia. The results are consistent with the hypothesis that the IFN-gamma-inducible iNOS pathway can contribute to chlamydial control in humans.
Igietseme
J U
JU
Department of Microbiology and Immunology, Morehouse School of Medicine, Atlanta, Georgia 30310, USA.
Uriri
I M
IM
Chow
M
M
Abe
E
E
Rank
R G
RG
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D002460:Cell Line; D002690:Chlamydia Infections / Q000276:immunology / Q000378:metabolism / Q000517:prevention & control; D002692:Chlamydia trachomatis / Q000187:drug effects* / Q000254:growth & development / Q000276:immunology*; D004848:Epithelium / Q000276:immunology / Q000378:metabolism; D005260:Female; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009569:Nitric Oxide / Q000378:metabolism / Q000494:pharmacology*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism
D000900:Anti-Bacterial Agents; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase