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

Abstract

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.

Comparison of Gamma Interferon-Mediated Antichlamydial Defense Mechanisms in Human and Mouse Cells

“…not encounter tryptophan starvation during the natural infection process. In contrast to what is seen with chlamydiae, IDO expression is important for clearance of Listeria monocytogenes infection of mouse placenta (31) and acute Toxoplasma gondii infection in mice (23). Clearly, the role of IDO in controlling infection in mice depends on a complex interplay between various factors, including infected tissue/cells, cytokines present in the environment, and the infecting pathogen.…”

Inhibition of experimental asthma by indoleamine 2,3-dioxygenase

“…The lung can develop strong, organ-specific antimicrobial activity while at the same time limiting the potential damage inflicted on the lung parenchyma by subsequent inflammatory processes. IDO has antimicrobial properties against a variety of intracellular pathogens, such as parasites (e.g., Toxoplasma gondii) (37), bacteria (e.g., Listeria monocytogenes) (38), mycobacteria (e.g., Mycobacterium avium) (12), and viruses (e.g., cytomegalovirus) (39). The inhibition of intracellular growth of these microorganisms can occur (a) by depletion of intracellular levels of the rarest amino acid, trp, which is essential for their growth, and/or (b) by the generation of antimicrobial trp metabolites.…”

Indoleamine 2,3-dioxygenase–expressing dendritic cells form suppurative granulomas following Listeria monocytogenes infection

“…Type I and II IFNs were previously described as potent inducers of IDO in macrophages (37), HeLa cells (38), and placentae (39). More recently, it was demonstrated that TNF-α, together with prostaglandin E 2 (PGE 2 ), can also induce IDO in DCs (33,40).…”