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Cited by 396

The DOI matches its Crossref record; 52 of the 52 references it cites were found in a registry or an index.

Acute Toxoplasmosis Leads to Lethal Overproduction of Th1 Cytokines

Open access
Mordue, Dana G, Monroy, Fernando, La Regina, Marie, Dinarello, Charles A, Sibley, L David·2001·The Journal of Immunology
DOI 10.4049/jimmunol.167.8.4574
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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.

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Metadata

Authors
Mordue, D. G., Monroy, F., La Regina, M., Dinarello, C. A., & Sibley, L. D.
Venue
The Journal of Immunology
Publisher
Oxford University Press (OUP)
Published
2001-10
Volume
167
Issue
8
Pages
4574-4584
ISSN
  • 0022-1767 (ISSN-L)
  • 1550-6606
DOI
10.4049/jimmunol.167.8.4574
OpenAlex
W2152283755
Cited by
396
References
52
FWCI
9.53
Type
journal article
Language
en
Open access
bronze

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