Role of Tryptophan in Gamma Interferon‐Mediated Chlamydial Persistence

Beatty, Wandy L.; Belanger, Theodore A.; Desai, A A; Morrison, Richard P.; Byrne, Gerald I.

doi:10.1111/j.1749-6632.1994.tb44274.x

Cited by 112 publications

(145 citation statements)

References 3 publications

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“…While IDO expression might be considered a relatively minor aspect of privilege in the context of transplantation, it might be significant for other immunological challenges with weaker antigens. In addition, up-regulation of IDO by inflammatory cytokines may operate as an immune protection mechanism in the eye, as depletion of tryptophan will inhibit growth of infectious pathogens [25,26], or more generally constitute a negative feedback loop to limit immune responses in the anterior chamber.…”

Section: Discussionmentioning

confidence: 99%

Function of indoleamine 2,3‐dioxygenase in corneal allograft rejection and prolongation of allograft survival by over‐expression

et al. 2006

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Indoleamine 2,3-dioxygenase (IDO) suppresses T cell responses by its action in catabolising tryptophan. It is important in maintenance of immune privilege in the placenta. We investigated the activity of IDO in the cornea, following corneal transplantation and the effect of IDO over-expression in donor corneal endothelium on the survival of corneal allografts. IDO expression was analysed and functional activity was quantified in normal murine cornea and in corneas following transplantation as allografts. Low levels of IDO, at both mRNA and protein levels, was detected in the normal cornea, up-regulated by IFN-c and TNF. Expression of IDO in cornea was significantly increased following corneal transplantation. However, inhibition of IDO activity in vivo had no effect on graft survival. Following IDO cDNA transfer, murine corneal endothelial cells expressed functional IDO, which was effective at inhibiting allogeneic T cell proliferation. Over-expression of IDO in donor corneal allografts resulted in prolonged graft survival. While, on one hand, our data indicate that IDO may augment corneal immune privilege, up-regulated IDO activity following cytokine stimulation may serve to inhibit inflammatory cellular responses. While increasing IDO mRNA expression was found in allogeneic corneas at rejection, over-expression in donor cornea was found to significantly extend survival of allografts.

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Section: Discussionmentioning

confidence: 99%

Function of indoleamine 2,3‐dioxygenase in corneal allograft rejection and prolongation of allograft survival by over‐expression

et al. 2006

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“…IFN-␥ has been shown to inhibit chlamydial strains in vitro in an IDO-mediated form (36,61). Although IDO Ϫ/Ϫ and WT mice have recently been shown to have similar susceptibility to infections with human or murine strains of C. trachomatis (62), a role for IDO in protection against C. pneumoniae remains to be investigated.…”

Section: Discussionmentioning

confidence: 99%

STAT1 Regulates IFN-αβ- and IFN-γ-Dependent Control of Infection withChlamydia pneumoniaeby Nonhemopoietic Cells

Rothfuchs

Trumstedt

Mattei

et al. 2006

The Journal of Immunology

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STAT1 mediates signaling in response to IFN-α, -β, and -γ, cytokines required for protective immunity against several viral, bacterial, and eukaryotic pathogens. The protective role of STAT1 in the control of intranasal infection with the obligate intracellular bacterium Chlamydia pneumoniae was analyzed. IFN-γ−/− or IFN-γ receptor (R)−/− mice were highly susceptible to infection with C. pneumoniae. We found that STAT1−/− mice were even more susceptible to C. pneumoniae than IFN-γ−/− or IFN-γR−/− mice. Phosphorylation of STAT1 was detected in the lungs of C. pneumoniae-infected wild-type, IFN-γR−/−, and IFN-αβR−/− mice, but not in mice lacking both IFN-αβR and IFN-γR. In line with this, IFN-αβR−/−/IFN-γR−/− mice showed increased susceptibility to infection compared with IFN-γR−/− mice. However, C. pneumoniae-infected IFN-αβR−/− or IFN regulatory factor 3−/− mice showed no increased susceptibility and similar IFN-γ expression compared with wild-type mice. CD4+ or CD8+ cells released IFN-γ in vivo and conferred protection against C. pneumoniae in a STAT1-independent manner. In contrast, STAT1 mediated a nonredundant protective role of nonhemopoietic cells but not of hemopoietic cells. Nonhemopoietic cells accounted for the expression of STAT1-mediated indoleamine 2, 3-dioxygenase and the p47 GTPase LRG-47, but not inducible NO synthase mRNA. In summary, we demonstrate that STAT1 mediates a cooperative effect of IFN-αβ and IFN-γ on nonhemopoietic cells, resulting in protection against C. pneumoniae.

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“…Although Chlamydia has a predilection for replicating in epithelial cells, it can also replicate in macrophages. Depletion of tryptophan in vitro by IDO drives the bacterium into a persistent altered life cycle in which the organism exists as an aberrant body (41). In the process of metabolizing tryptophan, IDO activity exerts antioxidant effects since the enzyme requires superoxide anion and generates several intermediate products that are potent radical scavengers as well as the energy generating NAD and NADP (42).…”

Section: Discussionmentioning

confidence: 99%

Indoleamine 2,3-Dioxygenase Is Regulated by IFN-γ in the Mouse Placenta DuringListeria monocytogenesInfection

Mackler¹,

Barber²,

Takikawa

et al. 2003

The Journal of Immunology

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The tryptophan-catabolizing enzyme indoleamine 2,3-dioxygenase (IDO) is expressed in macrophages that have been differentiated in the presence of CSF-1 and is important in the containment of intracellular pathogens. IDO also appears to play a role in suppression of T cell responses in a variety of contexts. In the placenta, its enzymatic activity is believed to establish a chemical barrier that protects the fetal allograft from T cell-mediated immune aggression. We have studied the regulation of IDO in the utero-placental unit of mice following infection with the Gram-positive, intracellular bacterium Listeria monocytogenes that has a predilection for replication in the decidua basalis. IDO mRNA and protein expression is enhanced in the utero-placental unit following infection with L. monocytogenes. However, in contrast to the human where IDO is expressed by the CSF-1R-positive syncytial trophoblast, IDO is not expressed in murine trophoblastic tissue but instead is found in stromal cells of the decidua basalis and metrial gland and following infection, in endothelial cells. Using mice carrying null mutations in cytokine/growth factor genes, we explored the regulation of IDO in the placenta. Consistent with the absence of CSF-1R expression in the IDO-expressing cells of mice, neither the basal levels of IDO nor its induction following infection is affected by the absence of CSF-1. However, although the basal level of IDO is normal, the enhanced expression during Listeriosis is completely abrogated in the absence of IFN-γ, a cytokine required for the resolution of this infection. These data suggest that IDO plays a role in resolving bacterial infection in the placenta while at the same time maintaining a barrier to T cells whose presence might result in fetal rejection.

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Role of Tryptophan in Gamma Interferon‐Mediated Chlamydial Persistence

Cited by 112 publications

References 3 publications

Function of indoleamine 2,3‐dioxygenase in corneal allograft rejection and prolongation of allograft survival by over‐expression

Function of indoleamine 2,3‐dioxygenase in corneal allograft rejection and prolongation of allograft survival by over‐expression

STAT1 Regulates IFN-αβ- and IFN-γ-Dependent Control of Infection withChlamydia pneumoniaeby Nonhemopoietic Cells

Indoleamine 2,3-Dioxygenase Is Regulated by IFN-γ in the Mouse Placenta DuringListeria monocytogenesInfection

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