3 years ago

Microbiome-mediated neutrophil recruitment via CXCR2 and protection from amebic colitis

Mamun Kabir, Koji Watanabe, Tuhinur Arju, Masud Alam, Stacey L. Burgess, Carol A. Gilchrist, Borna Mehrad, Shannon N. Moonah, Rashidul Haque, Brittany N. Schneider, Md Jashim Uddin, William A. Petri Jr., Emtiaz Ahmed, Mayuresh M. Abhyankar, Patcharin Pramoonjago, Zannatun Noor, Jeffrey R. Donowitz

by Koji Watanabe, Carol A. Gilchrist, Md Jashim Uddin, Stacey L. Burgess, Mayuresh M. Abhyankar, Shannon N. Moonah, Zannatun Noor, Jeffrey R. Donowitz, Brittany N. Schneider, Tuhinur Arju, Emtiaz Ahmed, Mamun Kabir, Masud Alam, Rashidul Haque, Patcharin Pramoonjago, Borna Mehrad, William A. Petri Jr.

The disease severity of Entamoeba histolytica infection ranges from asymptomatic to life-threatening. Recent human and animal data implicate the gut microbiome as a modifier of E. histolytica virulence. Here we have explored the association of the microbiome with susceptibility to amebiasis in infants and in the mouse model of amebic colitis. Dysbiosis occurred symptomatic E. histolytica infection in children, as evidenced by a lower Shannon diversity index of the gut microbiota. To test if dysbiosis was a cause of susceptibility, wild type C57BL/6 mice (which are innately resistant to E. histiolytica infection) were treated with antibiotics prior to cecal challenge with E. histolytica. Compared with untreated mice, antibiotic pre-treated mice had more severe colitis and delayed clearance of E. histolytica. Gut IL-25 and mucus protein Muc2, both shown to provide innate immunity in the mouse model of amebic colitis, were lower in antibiotic pre-treated mice. Moreover, dysbiotic mice had fewer cecal neutrophils and myeloperoxidase activity. Paradoxically, the neutrophil chemoattractant chemokines CXCL1 and CXCL2, as well as IL-1β, were higher in the colon of mice with antibiotic-induced dysbiosis. Neutrophils from antibiotic pre-treated mice had diminished surface expression of the chemokine receptor CXCR2, potentially explaining their inability to migrate to the site of infection. Blockade of CXCR2 increased susceptibility of control non-antibiotic treated mice to amebiasis. In conclusion, dysbiosis increased the severity of amebic colitis due to decreased neutrophil recruitment to the gut, which was due in part to decreased surface expression on neutrophils of CXCR2.

Publisher URL: http://journals.plos.org/plosone/article

DOI: 10.1371/journal.ppat.1006513

You might also like
Discover & Discuss Important Research

Keeping up-to-date with research can feel impossible, with papers being published faster than you'll ever be able to read them. That's where Researcher comes in: we're simplifying discovery and making important discussions happen. With over 19,000 sources, including peer-reviewed journals, preprints, blogs, universities, podcasts and Live events across 10 research areas, you'll never miss what's important to you. It's like social media, but better. Oh, and we should mention - it's free.

  • Download from Google Play
  • Download from App Store
  • Download from AppInChina

Researcher displays publicly available abstracts and doesn’t host any full article content. If the content is open access, we will direct clicks from the abstracts to the publisher website and display the PDF copy on our platform. Clicks to view the full text will be directed to the publisher website, where only users with subscriptions or access through their institution are able to view the full article.