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• W4313333851 endingPage "3436" @default.
• W4313333851 startingPage "3427" @default.
• W4313333851 abstract "Abstract TNF-α exerts its biologic activity through two distinct receptors, TNF receptor type 1 (TNFR1, p55) and TNF receptor type 2 (TNFR2, p75). To analyze their function in toxoplasmosis, we orally infected mice genetically deficient for TNFR1 (TNFR10/0), TNFR2 (TNFR20/0), or both TNF receptors (TNFR1/20/0), as well as wild-type (wt) mice with a low-virulent strain of Toxoplasma gondii. TNFR1/20/0 and TNFR10/0 mice succumbed to toxoplasmosis within 17 and 27 days, respectively, whereas TNFR20/0 and wt mice were equally resistant to acute toxoplasmosis. Histopathology attributed death of TNFR1/20/0 and TNFR10/0 mice to a fulminant necrotizing encephalitis. In addition, pneumonia contributed to the fatal outcome. The poor prognosis of TNFR1/20/0 and TNFR10/0 mice was reflected by a significantly increased parasitic load in the brain and lung as compared with TNFR20/0 and wt mice. Immunohistochemistry demonstrated a remarkable reduction of inducible nitric oxide synthase protein in brain and lung of TNFR1/20/0 and TNFR10/0 as compared with TNFR20/0 and wt mice. Reverse-transcribed PCR showed that in contrast to TNFR20/0 and wt mice, TNFR10/0 mice were unable to up-regulate inducible nitric oxide synthase mRNA transcripts in the course of infection, whereas intracerebral levels of IFN-γ, TNF-α, and IL-1β mRNA transcripts, recruitment of immune cells to the brain, and the amount of apoptotic cells in inflammatory foci did not differ significantly among the various experimental groups. These results illustrate that in Toxoplasma encephalitis, TNF-α-mediated immune responses are of crucial importance and that signaling through TNFR1, but not TNFR2, provides the stimulus required for the induction of protective nitric oxide." @default.
• W4313333851 created "2023-01-06" @default.
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• W4313333851 date "1998-04-01" @default.
• W4313333851 modified "2023-10-14" @default.
• W4313333851 title "Crucial Role of TNF Receptor Type 1 (p55), But Not of TNF Receptor Type 2 (p75), in Murine Toxoplasmosis" @default.
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• W4313333851 doi "https://doi.org/10.4049/jimmunol.160.7.3427" @default.
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