Acute toxoplasmosis leads to lethal overproduction of Th1 cytokines

D. G. Mordue, Fernando P Monroy, M. La Regina, C. A. Dinarello, L. D. Sibley

Research output: Contribution to journalArticle

222 Citations (Scopus)

Abstract

Virulence in Toxoplasma gondii is strongly influenced by the genotype of the parasite. Type I strains uniformly cause rapid death in mice regardless of the host genotype or the challenge dose. In contrast, the outcome of infections with type II strains is highly dependent on the challenge dose and the genotype of the host. To understand the basis of acute virulence in toxoplasmosis, we compared low and high doses of the RH strain (type I) and the ME49/PTG strain (type II) of T. gondii in outbred mice. Differences in virulence were reflected in only modestly different growth rates in vivo, and both strains disseminated widely to different tissues. The key difference in the virulent RH strain was the ability to reach high tissue burdens rapidly following a low dose challenge. Lethal infections caused by type I (RH) or type II (PTG) strain infections were accompanied by extremely elevated levels of Th1 cytokines in the serum, including IFN-γ, TNF-α, IL-12, and IL-18. Extensive liver damage and lymphoid degeneration accompanied the elevated levels of cytokines produced during lethal infection. Increased time of survival following lethal infection with the RH strain was provided by neutralization of IL-18, but not TNF-α or IFN-γ. Nonlethal infections with a low dose of type II PTG strain parasites were characterized by a modest induction of Th1 cytokines that led to control of infection and minimal damage to host tissues. Our findings establish that overstimulation of immune responses that are normally necessary for protection is an important feature of acute toxoplasmosis.

Original languageEnglish (US)
Pages (from-to)4574-4584
Number of pages11
JournalJournal of Immunology
Volume167
Issue number8
StatePublished - Oct 15 2001
Externally publishedYes

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Toxoplasmosis
Cytokines
Infection
Virulence
Interleukin-18
Genotype
Toxoplasma
Parasites
Interleukin-12
Infection Control
Cause of Death
Liver
Growth
Serum

ASJC Scopus subject areas

  • Immunology

Cite this

Mordue, D. G., Monroy, F. P., La Regina, M., Dinarello, C. A., & Sibley, L. D. (2001). Acute toxoplasmosis leads to lethal overproduction of Th1 cytokines. Journal of Immunology, 167(8), 4574-4584.

Acute toxoplasmosis leads to lethal overproduction of Th1 cytokines. / Mordue, D. G.; Monroy, Fernando P; La Regina, M.; Dinarello, C. A.; Sibley, L. D.

In: Journal of Immunology, Vol. 167, No. 8, 15.10.2001, p. 4574-4584.

Research output: Contribution to journalArticle

Mordue, DG, Monroy, FP, La Regina, M, Dinarello, CA & Sibley, LD 2001, 'Acute toxoplasmosis leads to lethal overproduction of Th1 cytokines', Journal of Immunology, vol. 167, no. 8, pp. 4574-4584.
Mordue DG, Monroy FP, La Regina M, Dinarello CA, Sibley LD. Acute toxoplasmosis leads to lethal overproduction of Th1 cytokines. Journal of Immunology. 2001 Oct 15;167(8):4574-4584.
Mordue, D. G. ; Monroy, Fernando P ; La Regina, M. ; Dinarello, C. A. ; Sibley, L. D. / Acute toxoplasmosis leads to lethal overproduction of Th1 cytokines. In: Journal of Immunology. 2001 ; Vol. 167, No. 8. pp. 4574-4584.
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