title: Increased sensitivity to tryptophan bioavailability is a positive adaptation by the human strains of Chlamydia pneumoniae.
abstract: One of the most significant activities induced by interferon-gamma against intracellular pathogens is the induction of IDO (indoleamine 2,3-dioxygenase) expression, which subsequently results in the depletion of tryptophan. We tested the hypothesis that human strains of Chlamydia pneumoniae are more sensitive to tryptophan limitation than animal C. pneumoniae strains. The human strains were significantly more sensitive to IFN-γ than the animal strains in a lung epithelia cell model (BEAS-2B), with exposure to 1 U ml(-1) IFN-γ resulting in complete loss of infectious yield of human strains, compared to the animal strains where reductions in infectious progeny were around 3.5-4.0 log. Strikingly, the IFN-γ induced loss of ability to form infectious progeny production was completely rescued by removal of the IFN-γ and addition of exogenous tryptophan for the human strains, but not the animal strains. In fact, a human heart strain was more capable of entering a non-infectious, viable persistent stage when exposed to IFN-γ and was also more effectively rescued, compared to a human respiratory strain. Exquisite susceptibility to IFN-γ, specifically due to tryptophan availability appears to be a core adaptation of the human C. pneumoniae strains, which may reflect the chronic nature of their infections in this host.
authors.affiliation: Institute of Health and Biomedical Innovation, School of Biomedical Sciences, Faculty of Health, Queensland University of Technology, 60 Musk Ave, Kelvin Grove, Qld, 4059, Australia.
authors.forename: Anu
authors.initials: A
authors.lastname: Chacko
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Barker
authors.forename: Kenneth W
authors.initials: KW
authors.lastname: Beagley
authors.forename: Mark P
authors.initials: MP
authors.lastname: Hodson
authors.forename: Manuel R
authors.initials: MR
authors.lastname: Plan
authors.forename: Peter
authors.initials: P
authors.lastname: Timms
authors.forename: Wilhelmina M
authors.initials: WM
authors.lastname: Huston
mesh_terms: D000818:Animals; D001682:Biological Availability; D002460:Cell Line; D023521:Chlamydophila Infections / Q000382:microbiology / Q000662:veterinary; D016993:Chlamydophila pneumoniae / Q000254:growth & development* / Q000302:isolation & purification / Q000378:metabolism*; D004847:Epithelial Cells / Q000378:metabolism / Q000382:microbiology; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology; D050296:Microbial Viability; D014364:Tryptophan / Q000378:metabolism*
chemical_list: D007371:Interferon-gamma; D014364:Tryptophan