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Updated: Jul 19, 2026

Cefoperazone-treated Mouse Model of Clinically-relevant Clostridium difficile Strain R20291
Published on: December 10, 2016
Porcine Monocyte DNA Traps Formed during Infection with Pathogenic Clostridioides difficile Strains
Jade Lawrence1, Paul Barrow2, Neil Foster3
1School of Veterinary Medicine and Science, University of Nottingham, Nottingham LE12 5RD, UK.
Abstract:
Clostridioides (Clostridium) difficile is an enteric pathogen of several mammalian species including man, frequently involving nosocomial resurgence, following oral administration of broad-spectrum antibiotics, but also with human-to-human infection occurring, and neonatal pigs with zoonotic transmission. To date, the immune response to C. difficile has mostly focused on neutrophils and cytokine/chemokines, particularly in human infection. The neonatal pig is now recognized as a valuable model for human infection. We show that porcine monocytes respond to C. difficile differently compared with many other bacterial infections. Infection of porcine monocytes with human C. difficile strains CD630 (Ribotype 078) or R20291 (Ribotype 027) for 3 or 24 h post-infection (pi) resulted in a lack of oxidative burst or nitrite ion production when compared to uninfected controls (p > 0.05). The survival dynamics of both CD630 and R20291 in monocytes were similar with intracellular bacterial numbers being similar at 3 h pi and 24 h pi (p > 0.05). However, we show that porcine monocytes entrap C. difficile via extracellular DNA traps. This process began as early as 3 h pi, and at 24 h pi the nuclei appeared to be depleted of DNA, although extracellular DNA was associated with the cell membrane. Our preliminary study also suggests that entrapment of C. difficile by extracellular DNA may occur via a process of monocyte etosis.
Insights
Porcine monocytes trap Clostridioides difficile bacteria using extracellular DNA traps, a process called etosis. This unique immune response differs from typical bacterial infections, offering insights into C. difficile pathogenesis.
Area of Science:
- Immunology
- Microbiology
- Veterinary Medicine
Background:
- Clostridioides difficile (C. difficile) is a significant enteric pathogen causing infections in humans and animals.
- Neonatal pigs serve as a valuable model for studying human C. difficile infections.
- Previous research on C. difficile immunity primarily focused on neutrophils and cytokines.
Purpose of the Study:
- To investigate the immune response of porcine monocytes to C. difficile infection.
- To compare the response of porcine monocytes to C. difficile with their response to other bacterial infections.
- To elucidate the mechanisms by which porcine monocytes interact with C. difficile.
Main Methods:
- Infection of porcine monocytes with C. difficile strains CD630 and R20291.
- Assessment of oxidative burst and nitrite ion production.
- Analysis of intracellular bacterial survival dynamics.
- Microscopic examination of monocyte-bacteria interaction and DNA trap formation.
Main Results:
- Porcine monocytes showed a lack of oxidative burst and nitrite production upon C. difficile infection.
- Intracellular survival of C. difficile strains CD630 and R20291 within monocytes was similar.
- Porcine monocytes effectively entrapped C. difficile using extracellular DNA traps, a process resembling etosis.
- DNA depletion was observed in monocyte nuclei, with extracellular DNA associated with the cell membrane.
Conclusions:
- Porcine monocytes exhibit a distinct immune response to C. difficile, characterized by etosis rather than oxidative burst or nitrite production.
- Extracellular DNA traps play a crucial role in the entrapment of C. difficile by porcine monocytes.
- This study highlights the neonatal pig model for understanding C. difficile pathogenesis and host-pathogen interactions.
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