Mechanisms of interferon induced inhibition of Toxoplasma gondii replication in human RPE cells

C. N. Nagineni, K. Pardhasaradhi, M. C. Martins, B. Detrick, J. J. Hooks

Research output: Contribution to journalArticlepeer-review

Abstract

Purpose. Toxoplasma gondii (T. gondii) infection induces retinochoroiditis in infants and adults and causes serious retinal diseases in immunosoppressed individuals. We have studied the mechanisms of interferon (IFN) actions on the replication of T. gondii in human RPE (HRPE) cells. Methods. Primary cell lines of HRPE were prepared from donor eyes. HRPE cultures pretreated with IFN were inoculated with tachyzoites of T. gondii and replication of the parasite was quantitated by counting the plaques and parasites released from the cells. Induction of Indoleamine 2,3-dioxygenase (IDO) was evaluated by RT-PCR and northern blot analysis. Results. Human rIFN-α,β,γ inhibited T. gondii replication in HRPE in a dose dependent manner. IFN-γ was the most active and completely inhibited T. gondii replication. This inhibition was reversed by pretreatment with mab to IFN-γ. Addition of L-tryptophan to IFN-γ treated cells significantly reversed the anti-toxoplasma effects of IFN-γ. RT-PCR and northern blot analysis of IFN-γ treated HRPE treated with IFN showed induction of IDO, an enzyme that converts tryptophan to keyneurinine. In contrast, IFN did not induce nitric oxide (NO) production by HRPE suggesting that IFN did not act through NO dependent mechanisms. Conclusions. IFN-γ inhibits replication of T. gondii in HRPE by inducing IDO and thereby depleting cellular tryptophan. an essential amino acid, required for the growth of parasites. This in vitro model of T. gondii replication in HRPE may be useful in evaluating the effects of cytokines and drugs on T. gondii replication within retina.

Original languageEnglish (US)
Pages (from-to)S373
JournalInvestigative Ophthalmology and Visual Science
Volume37
Issue number3
StatePublished - Feb 15 1996
Externally publishedYes

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

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