Signaling through interleukin-10 (IL-10) receptors on gut immune cells plays a critical role in protecting the gut lining and microbiota from disruption caused by whipworms, according to a study published January 31 in the open-access journal PLOS Pathogens by María Duque-Correa of the Wellcome Sanger Institute in the UK, and colleagues.
The human gut is home to millions of bacteria, collectively called the microbiota, and also to parasites such as whipworms, which cause a human disease called trichuriasis. Cells lining the gut host whipworms but also interact with gut immune cells to deploy measures that control or expel whipworms while maintaining a barrier to prevent microbial movement to organs such as the liver. Whipworms affect the composition of the microbiota, which in turn impacts the condition of the gut lining and the way in which immune cells are activated. In order to avoid tissue damage and disease, these interactions are tightly regulated. Using a mouse model, Duque-Correa and colleagues show that these interactions are regulated by signaling through a member of the IL-10 receptor family, IL-10R?, on gut immune cells.
Lack of this receptor on gut immune cells results in persistence of whipworms in the gut accompanied by uncontrolled inflammation that destroys the gut lining. This tissue damage is accompanied by the overgrowth of microbes that act as opportunistic pathogens. Moreover, the destruction of the gut barrier allows these bacteria to reach the liver, where they cause organ failure and fatal disease. Taken together, the findings emphasize the pivotal and complex role of IL-10R? signaling on immune cells in promoting microbiota homeostasis and maintaining the intestinal barrier during whipworm infections.
The authors note, "Our study reveals the master role of IL-10Ra in regulating the interactions between gut cells, the microbiota and whipworms that define the conditions for balanced parasitism. We discovered the absence of this crucial signalling pathway leads to uncontrolled inflammation that destroys the gut lining allowing microbes to invade and cause liver failure."
Funding: MADC has received funding from the European Union's Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant agreement No 656347(http://www.ec.europa.eu/research/mariecurieactions/). The 3i consortium was supported by Wellcome Trust grant  (http://www.immunophenotype.org). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Competing Interests: The authors have declared that no competing interests exist.
Citation: Duque-Correa MA, Karp NA, McCarthy C, Forman S, Goulding D, Sankaranarayanan G, et al. (2019) Exclusive dependence of IL-10Rα signalling on intestinal microbiota homeostasis and control of whipworm infection. PLoS Pathog 15(1): e1007265. https://doi.org/10.1371/journal.ppat.1007265
Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, United Kingdom
Lydia Becker Institute of Immunology and Inflammation, Wellcome Trust Centre for Cell Matrix Research and Faculty of Biology, Medicine and Health, University of Manchester, Manchester, United Kingdom
Department of Veterinary Medicine, University of Cambridge, Cambridge, United Kingdom
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