title: Surface layer proteins isolated from Clostridium difficile induce clearance responses in macrophages.
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.
authors.affiliation: Immunomodulation Research Group, School of Biotechnology, Dublin City University, Dublin 9, Ireland.
authors.forename: Laura E
authors.initials: LE
authors.lastname: Collins
authors.affiliation: Immunomodulation Research Group, School of Biotechnology, Dublin City University, Dublin 9, Ireland.
authors.forename: Mark
authors.initials: M
authors.lastname: Lynch
authors.affiliation: Immunomodulation Research Group, School of Biotechnology, Dublin City University, Dublin 9, Ireland.
authors.forename: Izabela
authors.initials: I
authors.lastname: Marszalowska
authors.affiliation: Immunomodulation Research Group, School of Biotechnology, Dublin City University, Dublin 9, Ireland.
authors.forename: Maja
authors.initials: M
authors.lastname: Kristek
authors.affiliation: School of Biotechnology, Dublin City University, Ireland.
authors.forename: Keith
authors.initials: K
authors.lastname: Rochfort
authors.affiliation: Molecular Evolution Group, School of Biotechnology, Dublin City University, Ireland.
authors.forename: Mary
authors.initials: M
authors.lastname: O'Connell
authors.affiliation: Institute of Molecular Medicine, Trinity College Dublin, Ireland.
authors.forename: Henry
authors.initials: H
authors.lastname: Windle
authors.affiliation: Institute of Molecular Medicine, Trinity College Dublin, Ireland.
authors.forename: Dermot
authors.initials: D
authors.lastname: Kelleher
authors.affiliation: Immunomodulation Research Group, School of Biotechnology, Dublin City University, Dublin 9, Ireland. Electronic address: christine.loscher@dcu.ie.
authors.forename: Christine E
authors.initials: CE
authors.lastname: Loscher
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000276:immunology*; D002465:Cell Movement; D016360:Clostridioides difficile / Q000276:immunology*; D016207:Cytokines / Q000378:metabolism; D020935:MAP Kinase Signaling System; D008264:Macrophages / Q000276:immunology* / Q000382:microbiology*; D008562:Membrane Glycoproteins / Q000276:immunology*; D051379:Mice; D010587:Phagocytosis
chemical_list: D001426:Bacterial Proteins; D016207:Cytokines; D008562:Membrane Glycoproteins; C055764:S-layer proteins
keywords: Clostridium difficile; Cytokine; Macrophage; Phagocytosis; Surface layer proteins; p38