Rxivist logo

Rxivist combines preprints from bioRxiv with data from Twitter to help you find the papers being discussed in your field. Currently indexing 57,313 bioRxiv papers from 263,927 authors.

Exclusive dependence of IL-10Rα signalling on intestinal microbiota homeostasis and control of whipworm infection

By Maria Adelaida Duque-Correa, Natasha A Karp, Catherine McCarthy, Simon Forman, David Goulding, Geetha Sankaranarayanan, Timothy P Jenkins, Adam J Reid, Hilary P. Browne, Emma L Cambridge, Carmen Ballesteros Reviriego, Werner Müller, Cinzia Cantacessi, Gordon Dougan, Richard K Grencis, Matthew Berriman, The 3i consortium

Posted 08 Aug 2018
bioRxiv DOI: 10.1101/388173 (published DOI: 10.1371/journal.ppat.1007265)

The whipworm Trichuris trichiura is a soil-transmitted helminth that dwells in the epithelium of the caecum and proximal colon of their hosts causing the human disease, trichuriasis. Trichuriasis is characterized by colitis attributed to the inflammatory response elicited by the parasite while tunnelling through intestinal epithelial cells (IECs). The IL-10 family of receptors, comprising combinations of subunits IL-10Rα, IL-10Rβ, IL-22Rα and IL-28Rα, modulates intestinal inflammatory responses. Here we carefully dissected the role of these subunits in the resistance of mice to infection with T. muris, a mouse model of the human whipworm T. trichiura. Our findings demonstrate that whilst IL-22Rα and IL-28Rα are dispensable in the host response to whipworms, IL-10 signalling through IL-10Rα and IL-10Rβ is essential to control caecal pathology, worm expulsion and survival during T. muris infections. We show that deficiency of IL-10, IL-10Rα and IL-10Rβ results in dysbiosis of the caecal microbiota characterised by expanded populations of opportunistic bacteria of the families Enterococcaceae and Enterobacteriaceae. Moreover, breakdown of the epithelial barrier after whipworm infection in IL-10, IL-10Rα and IL-10Rβ-deficient mice, allows the translocation of these opportunistic pathogens or their excretory products to the liver causing organ failure and lethal disease. Importantly, bone marrow chimera experiments indicate that signalling through IL-10Rα and IL-10Rβ in haematopoietic cells, but not IECs, is crucial to control worm expulsion and immunopathology. These findings are supported by worm expulsion upon infection of conditional mutant mice for the IL-10Rα on IECs. Our findings emphasize the pivotal role of systemic IL-10Rα signalling on immune cells in promoting microbiota homeostasis and maintaining the intestinal epithelial barrier, thus preventing immunopathology during whipworms infections.

Download data

  • Downloaded 228 times
  • Download rankings, all-time:
    • Site-wide: 36,771 out of 57,313
    • In immunology: 716 out of 1,363
  • Year to date:
    • Site-wide: 32,757 out of 57,313
  • Since beginning of last month:
    • Site-wide: 17,336 out of 57,313

Altmetric data


Downloads over time

Distribution of downloads per paper, site-wide


Sign up for the Rxivist weekly newsletter! (Click here for more details.)


News