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PMID: 8063385 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Tryptophan depletion as a mechanism of gamma interferon-mediated chlamydial persistence.

Infection and immunity ·Vol. 62 ·No. 9 ·1994-09-00 ·Pages 3705-11

Beatty WL, Belanger TA, Desai AA, Morrison RP, Byrne GI

Abstract

Previous studies have shown that the immune-regulated cytokine gamma interferon (IFN-gamma) activates host cells to restrict intracellular growth of the bacterial pathogen Chlamydia trachomatis by induction of the tryptophan-catabolizing enzyme indoleamine 2,3-dioxygenase (IDO). Recently, subinhibitory levels of IFN-gamma were used to generate an in vitro persistent chlamydial infection characterized by large aberrant, noninfectious reticulate bodies from which infectious progeny could be recovered following the removal of IFN-gamma. Studies were done to determine if the mechanism functioning to induce chlamydiae to enter a persistent state in the presence of low levels of IFN-gamma was similar to that reported to inhibit chlamydial growth. Host cells treated with levels of IFN-gamma required to induce persistence were assessed for IDO activity by high-performance liquid chromatography analysis of tryptophan and its catabolic products. Substantial tryptophan catabolism was detected in acid-soluble cellular pools, indicating that the intracellular availability of this essential amino acid was limited under these conditions. In addition, a mutant cell line responsive to IFN-gamma but deficient in IDO activity was shown to support C. trachomatis growth, but aberrant organisms were not induced in response to IFN-gamma treatment. Analyses of infected cells cultured in medium with incremental levels of exogenous tryptophan indicated that persistent growth was induced by reducing the amount of this essential amino acid. These studies confirmed that nutrient deprivation by IDO-mediated tryptophan catabolism was the mechanism by which IFN-gamma mediates persistent growth of C. trachomatis.

MeSH Terms
Chlamydia trachomatis/drug effects,growth & development Cycloheximide/pharmacology Enzyme Induction HeLa Cells Humans Indoleamine-Pyrrole 2,3,-Dioxygenase Interferon-gamma/pharmacology Tryptophan/physiology Tryptophan Oxygenase/biosynthesis
Chemicals
Indoleamine-Pyrrole 2,3,-Dioxygenase Interferon-gamma Tryptophan Cycloheximide Tryptophan Oxygenase
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Beatty W L
Department of Medical Microbiology and Immunology, University of Wisconsin, Madison 53706.
Belanger T A
Desai A A
Morrison R P
Byrne G I
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Article Info
Journal
Infection and immunity
Abbr.
Infect Immun
ISSN
0019-9567
DOI
10.1128/iai.62.9.3705-3711.1994
Published
1994-09-00
Pages
3705-11
Language
English
Region
United States
NLM ID
0246127
PMCID
PMC303021
Subset
IM
Grants
NIAID NIH HHS · R01 AI019782 · United States
NIAID NIH HHS · AI 19782 · United States
NIAID NIH HHS · AI 34617 · United States
External Links
PubMed source DOI: 10.1128/iai.62.9.3705-3711.1994 PMC Full Text View journal details
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