Infection-Induced Intestinal Dysbiosis Is Mediated by Macrophage Activation and Nitrate Production

Shuai Wang(Lanzhou Veterinary Research Institute), Ayah El‐Fahmawi(University of Pennsylvania), David A. Christian(University of Pennsylvania), Qun Fang(University of Pennsylvania), Enrico Radaelli(University of Pennsylvania), Longfei Chen(University of Pennsylvania), Megan C. Sullivan(University of Pennsylvania), Ana M. Misic(University of Pennsylvania), Jodi A. Ellringer(University of Pennsylvania), Xing-Quan Zhu(Lanzhou Veterinary Research Institute), Sebastian Winter(The University of Texas Southwestern Medical Center), Christopher A. Hunter(University of Pennsylvania), Daniel P. Beiting(University of Pennsylvania)
mBio
May 25, 2019
Cited by 88Open Access
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Abstract

Toxoplasma gondii is a protozoan parasite and a leading cause of foodborne illness. Infection is initiated when the parasite invades the intestinal epithelium, and in many host species, this leads to intense inflammation and a dramatic disruption of the normal microbial ecosystem that resides in the healthy gut (the so-called microbiome). One characteristic change in the microbiome during infection with Toxoplasma —as well as numerous other pathogens—is the overgrowth of Escherichia coli or similar bacteria and a breakdown of commensal containment leading to seeding of peripheral organs with gut bacteria and subsequent sepsis. Our findings provide one clear explanation for how this process is regulated, thereby improving our understanding of the relationship between parasite infection, inflammation, and disease. Furthermore, our results could serve as the basis for the development of novel therapeutics to reduce the potential for harmful bacteria to bloom in the gut during infection.


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