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

mBio - Tập 10 Số 3 - 2019
Shuai Wang1,2, Ayah El‐Fahmawi1, David A. Christian1, Qun Fang1, Enrico Radaelli1, Longfei Chen1, Megan C. Sullivan1, Ana M. Misic1, Jodi A. Ellringer1, Xing Zhu2, Sebastian Winter3, Christopher A. Hunter1, Daniel P. Beiting1
1Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania USA
2State 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
3Department of Microbiology, University of Texas Southwestern Medical Center, Dallas, Texas, USA

Tóm tắt

Toxoplasma gondiiis 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 withToxoplasma—as well as numerous other pathogens—is the overgrowth ofEscherichia colior 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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Tài liệu tham khảo

Robertson LJ. 2018. The global impact of foodborne parasites, p 325–340. In Ortega YR, Sterling CR (ed), Foodborne parasites. Springer International Publishing, Cham, Switzerland.

10.1038/nri3598

10.1038/nrmicro2858

Hill DE, Dubey JP. 2018. Toxoplasma gondii, p 119–138. In Ortega YR, Sterling CR (ed), Foodborne parasites. Springer International Publishing, Cham, Switzerland.

10.1590/S0074-02762009000200015

10.1016/S0171-2985(99)80063-1

10.1128/IAI.00472-09

10.1038/mi.2009.105

10.1016/j.chom.2013.08.003

10.1038/nm.3189

10.1046/j.1365-3024.1999.00237.x

10.1038/ni.2508

10.1016/j.immuni.2015.01.011

10.1084/jem.20090900

10.1038/mi.2011.31

10.1038/icb.2011.93

10.1086/338006

10.1371/journal.pntd.0002880

10.1038/mi.2017.20

10.3855/jidc.8179

10.1038/srep25255

10.1080/16512235.2017.1335165

10.1371/journal.pgen.1005658

10.1126/science.1220961

10.4049/jimmunol.177.12.8785

10.1371/journal.pone.0041594

10.1016/j.chom.2018.01.001

10.1073/pnas.94.25.13955

10.1006/clin.1993.1062

Hayashi S, Chan CC, Gazzinelli R, Roberge FG. 1996. Contribution of nitric oxide to the host parasite equilibrium in toxoplasmosis. J Immunol 156:1476–1481.

10.1126/science.1232467

10.1038/embor.2013.27

10.1128/IAI.01722-14

10.1371/journal.ppat.1003706

Gazzinelli RT, Eltoum I, Wynn TA, Sher A. 1993. Acute cerebral toxoplasmosis is induced by in vivo neutralization of TNF-alpha and correlates with the down-regulated expression of inducible nitric oxide synthase and other markers of macrophage activation. J Immunol 151:3672–3681.

10.1038/nrd2222

Neidhardt FC, Curtiss R, III, Ingraham JL, Lin ECC, Low KB, Magasanik B, Reznikoff WS, Riley M, Schaechter M, Umbarger HE (ed). 1996. Escherichia coli and Salmonella: cellular and molecular biology, 2nd ed. ASM Press, Washington, DC.

10.1556/EuJMI.3.2013.2.6

10.1016/j.bbabio.2012.11.007

Ohmori Y, Hamilton TA. 2001. Requirement for STAT1 in LPS-induced gene expression in macrophages. J Leukoc Biol 69:598–604.

10.1046/j.1365-2567.2003.01620.x

10.1152/ajpgi.00467.2004

10.4049/jimmunol.164.12.6166

10.1073/pnas.062578399

10.1016/j.chom.2017.01.005

10.1016/j.chom.2018.01.005

10.4110/in.2014.14.6.277

10.1128/AEM.01641-16

10.1128/IAI.00948-16

10.1186/1476-0711-6-17

10.1093/jpids/piw082

10.1371/journal.ppat.1007295

10.1126/science.1187703

10.1126/science.1256942

10.1002/ibd.21299

10.4161/gmic.32155

10.1016/j.immuni.2015.09.012

10.1593/neo.10716

National Research Council. 2011. Guide for the care and use of laboratory animals, 8th ed. National Academies Press, Washington, DC.

10.1016/j.jneuroim.2005.04.018

10.1016/0378-1119(91)90366-J

10.1002/0471142735.im0401s01

10.1128/AEM.01043-13

10.1002/0471250953.bi1007s36

10.1128/AEM.01541-09

10.1371/journal.pone.0061217

10.1186/s13059-014-0550-8

10.1093/bioinformatics/btp352

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