Surface layer proteins from Clostridium difficile induce inflammatory and regulatory cytokines in human monocytes and dendritic cells.
Clostridium difficile, an etiological agent of most cases of antibiotic-associated diarrhea, exerts its pathological action mainly by the activity of toxin A and toxin B. Less known is the role that S-layer proteins (SLPs), predominant surface components of the bacterium, may play in pathogenesis. Here, we evaluate the ability of SLPs to modulate the function of human monocytes and dendritic cells (DC) and to induce inflammatory and regulatory cytokines, influencing the natural and adaptive immune response. To this aim, SLPs were extracted from the clinical isolate C253 and characterized for their effects on immune cells. SLPs induced the release of elevated amounts of interleukin (IL)-1beta and IL-6 pro-inflammatory cytokines by resting monocytes, induced maturation of human monocyte-derived DC (MDDC), and enhanced proliferation of allogeneic T cells. C253-SLP-treated MDDC also secreted large amounts of IL-10 and IL-12p70 and induced a mixed Th1/Th2 orientation of immune response in naïve CD4 T cells. In conclusion, C. difficile SLPs may contribute to the pathogenicity of the bacterium by perturbing the fine balance of inflammatory and regulatory cytokines. These data are of interest also in the light of the possible use of SLPs in a multicomponent vaccine against C. difficile infections for high-risk patients.
Ausiello
Clara Maria
CM
Department of Infectious, Parasitic and Immune-mediated Diseases, Anti-Infectious Immunity Unit, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, Italy. ausiello@iss.it <ausiello@iss.it>
Cerquetti
Marina
M
Fedele
Giorgio
G
Spensieri
Fabiana
F
Palazzo
Raffaella
R
Nasso
Maria
M
Frezza
Simona
S
Mastrantonio
Paola
P
D001426:Bacterial Proteins / Q000276:immunology* / Q000302:isolation & purification; D049109:Cell Proliferation; D016360:Clostridioides difficile / Q000276:immunology*; D016207:Cytokines / Q000096:biosynthesis*; D003713:Dendritic Cells / Q000276:immunology*; D008213:Lymphocyte Activation; D008562:Membrane Glycoproteins / Q000276:immunology* / Q000302:isolation & purification; D009000:Monocytes / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology
D001426:Bacterial Proteins; D016207:Cytokines; D008562:Membrane Glycoproteins; C055764:S-layer proteins