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Clostridioides difficile Toxin B Activates Group 3 Innate Lymphocytes.

Rosemary L Pope1, Alisha Chitrakar1, Prakash Sah1

  • 1Department of Microbiology and Immunology, College of Medicine, The University of Oklahoma Health Sciences Centergrid.266902.9, Oklahoma City, Oklahoma, USA.

Infection and Immunity
|April 4, 2022
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Summary

Clostridioides difficile toxin B directly activates Group 3 innate lymphocytes (ILC3s) to produce interleukin-22 (IL-22). This occurs by inhibiting the small GTPase Cdc42, revealing a key immune response mechanism.

Keywords:
C. difficileIL-22ILC3TcdBtoxins

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Area of Science:

  • Immunology
  • Microbiology
  • Gastroenterology

Background:

  • Group 3 innate lymphocytes (ILC3s) are crucial immune cells in mucosal tissues, particularly the gut.
  • ILC3s produce interleukin-22 (IL-22), a cytokine vital for epithelial protection during infection and inflammation.
  • The precise mechanisms of ILC3 activation and IL-22 production in response to pathogens like Clostridioides difficile remain unclear.

Purpose of the Study:

  • To elucidate the novel mechanisms of ILC3 activation by Clostridioides difficile.
  • To identify how ILC3s sense infection and initiate an immune response through IL-22 production.

Main Methods:

  • Investigated the direct effects of Clostridioides difficile Toxin B (TcdB) on ILC3s.
  • Utilized pharmacological inhibition of small GTPases, specifically Cdc42.
  • Performed gene expression analysis to identify modulated inflammatory pathways.

Main Results:

  • Clostridioides difficile Toxin B directly induced IL-22 production in ILC3s.
  • TcdB's glucosyltransferase activity, which inhibits small GTPases, was essential for IL-22 induction.
  • Inhibiting Cdc42 enhanced IL-22 production, identifying Cdc42 as a negative regulator of ILC3 activation.
  • TcdB treatment altered the expression of inflammation-related genes in ILC3s.

Conclusions:

  • Clostridioides difficile toxin-mediated inhibition of Cdc42 is a novel mechanism for activating ILC3s.
  • This pathway highlights how ILC3s are recruited into the immune response against C. difficile.
  • Findings provide critical insights into the innate immune defense against gut pathogens.