title: Immunomodulatory activities of surface-layer proteins obtained from epidemic and hypervirulent Clostridium difficile strains.
abstract: Surface-layer proteins (SLPs) have been detected in all Clostridium difficile strains and play a role in adhesion, although an involvement in the inflammatory process may also be supposed, as they cover the bacterial surface and are immunodominant antigens. The aim of this study was to evaluate the immunomodulatory properties of SLPs obtained from hypervirulent and epidemic (H/E) or non-H/E C. difficile strains, to try to determine whether they contribute to hypervirulence. SLPs were purified from H/E PCR ribotype 027 and 001 and non-H/E PCR ribotype 012 C. difficile strains, and the ability to modulate these properties was studied in human ex vivo models of monocytes and monocyte-derived dendritic cells (MDDCs). The results indicated that SLPs were able to induce immunomodulatory cytokines [interleukin (IL)-1β, IL-6 and IL-10] in monocytes. SLPs induced maturation of MDDCs, which acquired enhanced antigen-presenting activity, a crucial function of the mature stage. SLP-primed MDDCs expressed high levels of IL-10, an important regulatory cytokine. No significant differences were found in the activation induced in monocytes and MDDCs by SLP preparations from H/E and non-H/E strains. Overall, these findings show an important role for SLPs in modulation of the immune response to C. difficile. However, SLPs from H/E strains did not show a specific immunomodulatory pattern compared with SLPs from non-H/E strains, suggesting that SLPs are not involved in the increased severity of infection peculiar to H/E strains.
authors.affiliation: Department of Infectious, Parasitic and Immune-Mediated Diseases, Istituto Superiore di Sanità, Rome, Italy.
authors.forename: Manuela
authors.initials: M
authors.lastname: Bianco
authors.affiliation: Department of Infectious, Parasitic and Immune-Mediated Diseases, Istituto Superiore di Sanità, Rome, Italy.
authors.forename: Giorgio
authors.initials: G
authors.lastname: Fedele
authors.affiliation: Department of Infectious, Parasitic and Immune-Mediated Diseases, Istituto Superiore di Sanità, Rome, Italy.
authors.forename: Adriano
authors.initials: A
authors.lastname: Quattrini
authors.affiliation: Department of Infectious, Parasitic and Immune-Mediated Diseases, Istituto Superiore di Sanità, Rome, Italy.
authors.forename: Patrizia
authors.initials: P
authors.lastname: Spigaglia
authors.affiliation: Department of Infectious, Parasitic and Immune-Mediated Diseases, Istituto Superiore di Sanità, Rome, Italy.
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Barbanti
authors.affiliation: Department of Infectious, Parasitic and Immune-Mediated Diseases, Istituto Superiore di Sanità, Rome, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Mastrantonio
authors.affiliation: Department of Infectious, Parasitic and Immune-Mediated Diseases, Istituto Superiore di Sanità, Rome, Italy.
authors.forename: Clara M
authors.initials: CM
authors.lastname: Ausiello
mesh_terms: D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D016360:Clostridioides difficile / Q000145:classification / Q000235:genetics / Q000378:metabolism* / Q000472:pathogenicity*; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects*; D015964:Gene Expression Regulation, Bacterial / Q000502:physiology; D006801:Humans; D007155:Immunologic Factors / Q000235:genetics / Q000378:metabolism; D009000:Monocytes / Q000378:metabolism; D021521:Ribotyping; D013601:T-Lymphocytes / Q000187:drug effects*; D014774:Virulence
chemical_list: D001426:Bacterial Proteins; D016207:Cytokines; D007155:Immunologic Factors