Inherent oxidative stress in the Lewis rat is associated with resistance to toxoplasmosis

William H. Witola, Chi Yong Kim, Xuejin Zhang

Research output: Contribution to journalArticle

Abstract

The course of Toxoplasma gondii infection in rats closely resembles that in humans. However, compared to the Brown Norway (BN) rat, the Lewis (LEW) rat is extremely resistant to T. gondii infection. Thus, we performed RNA sequencing analysis of the LEW rat versus the BN rat, with or without T. gondii infection, in order to unravel molecular factors directing robust and rapid early T. gondii-killing mechanisms in the LEW rat. We found that compared to the uninfected BN rat, the uninfected LEW rat has inherently higher transcript levels of cytochrome enzymes (Cyp2d3, Cyp2d5, and Cybrd1, which catalyze generation of reactive oxygen species [ROS]), with concomitant higher levels of ROS. Interestingly, despite having higher levels of ROS, the LEW rat had lower transcript levels for antioxidant enzymes (lactoperoxidase, microsomal glutathione S-transferase 2 and 3, glutathione S-transferase peroxidase kappa 1, and glutathione peroxidase) than the BN rat, suggesting that the LEW rat maintains cellular oxidative stress that it tolerates. Corroboratively, we found that scavenging of superoxide anion by Mn(III) tetrakis (4-benzoic acid) porphyrin (MnTBAP) decreased the refractoriness of LEW rat peritoneal cells to T. gondii infection, resulting in proliferation of parasites in LEW rat peritoneal cells which, in turn, led to augmented cell death in the infected cells. Together, our results indicate that the LEW rat maintains inherent cellular oxidative stress that contributes to resistance to invading T. gondii, and they thus unveil new avenues for developing therapeutic agents targeting induction of host cell oxidative stress as a mechanism for killing T. gondii.

Original languageEnglish (US)
Article numbere00289-17
JournalInfection and Immunity
Volume85
Issue number10
DOIs
StatePublished - 2017

Fingerprint

Toxoplasmosis
Oxidative Stress
Toxoplasma
Reactive Oxygen Species
Glutathione Transferase
Enzymes
Lactoperoxidase
RNA Sequence Analysis
Benzoic Acid
Porphyrins
Cytochromes
Glutathione Peroxidase
Superoxides
Peroxidase
Parasites
Cell Death
Antioxidants

Keywords

  • Brown Norway rat
  • Cytochrome enzymes
  • Innate immunity
  • Lewis rat
  • Oxidative stress
  • Toxoplasma gondii resistance

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Immunology
  • Infectious Diseases

Cite this

Inherent oxidative stress in the Lewis rat is associated with resistance to toxoplasmosis. / Witola, William H.; Kim, Chi Yong; Zhang, Xuejin.

In: Infection and Immunity, Vol. 85, No. 10, e00289-17, 2017.

Research output: Contribution to journalArticle

Witola, William H.; Kim, Chi Yong; Zhang, Xuejin / Inherent oxidative stress in the Lewis rat is associated with resistance to toxoplasmosis.

In: Infection and Immunity, Vol. 85, No. 10, e00289-17, 2017.

Research output: Contribution to journalArticle

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