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

Author:

Wang Shuai12,El-Fahmawi Ayah1,Christian David A.1,Fang Qun1,Radaelli Enrico1,Chen Longfei1,Sullivan Megan C.1,Misic Ana M.1,Ellringer Jodi A.1,Zhu Xing-Quan2,Winter Sebastian E.3ORCID,Hunter Christopher A.1ORCID,Beiting Daniel P.1ORCID

Affiliation:

1. Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA

2. State Key Laboratory of Veterinary Etiological Biology, Key Laboratory of Veterinary Parasitology of Gansu Province, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, Gansu, China

3. Department of Microbiology, University of Texas Southwestern Medical Center, Dallas, Texas, USA

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.

Funder

HHS | NIH | National Institute of Allergy and Infectious Diseases

Publisher

American Society for Microbiology

Subject

Virology,Microbiology

Reference68 articles.

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5. Small intestinal inflammation following oral infection with Toxoplasma gondii does not occur exclusively in C57BL/6 mice: review of 70 reports from the literature

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