Effect of cytokines on growth of Toxoplasma gondii in murine astrocytes

S. K. Halonen, F. C. Chiu, Louis M. Weiss

Research output: Contribution to journalArticle

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Abstract

Cytokines play a significant role in the regulation of Toxoplasma gondii in the central nervous system. Cytokine-activated microglia are important host defense cells in central nervous system infections. Recent evidence indicates that astrocytes can also be activated by cytokines to inhibit intracellular pathogens. In this study, we examined the effect of gamma interferon (IFN-γ), tumor necrosis factor alpha (TNF-α), interleukin-6 (IL- 6), and IL-1 on the growth of T. gondii in a primary murine astrocyte culture. Pretreatment of astrocytes with IFN-γ resulted in 65% inhibition of T. gondii growth. Neither TNF-α, IL-1, nor IL-6 alone had any effect on T. gondii growth. IFN-γ, in combination with either TNF-α, IL-1, or IL-6 caused a 75 to 80% inhibition of growth. While nitric oxide was produced by astrocytes treated with these cytokines, inhibition of T. gondii growth was not reversed by the addition of the nitric oxide synthase inhibitor N(G)- monomethyI-L-arginine. Furthermore, IFN-γ in combination with IL-1, IL-6, or TNF-α also induced inhibition in astrocytes derived from syngeneic mice deficient in the enzyme inducible nitric oxide synthase. This finding suggests that the mechanism of cytokine inhibition is not nitric oxide mediated. Similarly, the addition of tryptophan had no effect on inhibition, indicating thai the mechanism was not mediated via induction of the enzyme indoleamine 2,3-dioxygenase. The mechanism of inhibition remains to be elucidated. Results from this study demonstrate that cytokine-activated astrocytes are capable of significantly inhibiting the growth of T. gondii. These data indicate that astrocytes may be important host defense cells in controlling toxoplasmosis in the brain.

Original languageEnglish (US)
Pages (from-to)4989-4993
Number of pages5
JournalInfection and Immunity
Volume66
Issue number10
StatePublished - 1998

Fingerprint

Toxoplasma
Astrocytes
Cytokines
Interleukin-1
Growth
Interleukin-6
Interferons
Nitric Oxide
Indoleamine-Pyrrole 2,3,-Dioxygenase
Central Nervous System Infections
Enzyme Induction
Toxoplasmosis
Microglia
Nitric Oxide Synthase Type II
Nitric Oxide Synthase
Tryptophan
Interferon-gamma
Arginine
Central Nervous System
Tumor Necrosis Factor-alpha

ASJC Scopus subject areas

  • Immunology

Cite this

Effect of cytokines on growth of Toxoplasma gondii in murine astrocytes. / Halonen, S. K.; Chiu, F. C.; Weiss, Louis M.

In: Infection and Immunity, Vol. 66, No. 10, 1998, p. 4989-4993.

Research output: Contribution to journalArticle

Halonen, S. K. ; Chiu, F. C. ; Weiss, Louis M. / Effect of cytokines on growth of Toxoplasma gondii in murine astrocytes. In: Infection and Immunity. 1998 ; Vol. 66, No. 10. pp. 4989-4993.
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