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Surface layer proteins isolated from Clostridium difficile induce clearance responses in macrophages.

Authors
  • Collins, Laura E1
  • Lynch, Mark1
  • Marszalowska, Izabela1
  • Kristek, Maja1
  • Rochfort, Keith2
  • O'Connell, Mary3
  • Windle, Henry4
  • Kelleher, Dermot4
  • Loscher, Christine E5
  • 1 Immunomodulation Research Group, School of Biotechnology, Dublin City University, Dublin 9, Ireland. , (Ireland)
  • 2 School of Biotechnology, Dublin City University, Ireland. , (Ireland)
  • 3 Molecular Evolution Group, School of Biotechnology, Dublin City University, Ireland. , (Ireland)
  • 4 Institute of Molecular Medicine, Trinity College Dublin, Ireland. , (Ireland)
  • 5 Immunomodulation Research Group, School of Biotechnology, Dublin City University, Dublin 9, Ireland. Electronic address: [email protected] , (Ireland)
Type
Published Article
Journal
Microbes and infection
Publication Date
May 01, 2014
Volume
16
Issue
5
Pages
391–400
Identifiers
DOI: 10.1016/j.micinf.2014.02.001
PMID: 24560642
Source
Medline
Keywords
License
Unknown

Abstract

Clostridium difficile is the leading cause of hospital-acquired diarrhoea worldwide, and if the bacterium is not cleared effectively it can pose a risk of recurrent infections and complications such as colitis, sepsis and death. In this study we demonstrate that surface layer proteins from the one of the most frequently acquired strains of C. difficile, activate mechanisms in murine macrophage in vitro that are associated with clearance of bacterial infection. Surface layer proteins (SLPs) isolated from C. difficile induced the production of pro-inflammatory cytokines and chemokines and increased macrophage migration and phagocytotic activity in vitro. Furthermore, we also observed up-regulation of a number of cell surface markers on the macrophage, which are important in pathogen recognition and antigen presentation. The effects of SLPs on macrophages were reversed in the presence of a p38 inhibitor, indicating the potential importance of this signalling protein in how SLP activates the immune system. In conclusion this study shows that surface layer proteins from a common strain of C. difficile can activate a clearance response in macrophage and suggests that these proteins are important in clearance of C. difficile infection. Understanding how the immune system clears C. difficile infection could offer important insights for new treatment strategies.

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