title: The role of programmed death ligand 1 pathway in persistent biomaterial-associated infections.
abstract: Staphylococcus epidermidis is commonly involved in biomaterial-associated infections. Bacterial small colony variants (SCV) seem to be well adapted to persist intracellularly in professional phagocytes evading the host immune response. We studied the expression of PD-L1/L2 on macrophages infected with clinical isolates of S. epidermidis SCV and their parent wild type (WT) strains. The cytokine pattern which is triggered by the examined strains was also analysed. In the study, we infected macrophages with S. epidermidis WT and SCV strains. Persistence and release from macrophages were monitored via lysostaphin protection assays. Moreover, the effect of IFN-γ pre-treatment on bacterial internalisation was investigated. Expression of PD-L1/L2 molecules was analysed with the use of FACS. Inflammatory reaction was measured by IL-10, TNF-α ELISAs, and transcriptional induction of TNF-α. Our study revealed that clinical SCV isolates were able to persist and survive in macrophages for at least 3 days with a low cytotoxic effect and a reduced proinflammatory response as compared to WT strains. Bacteria upregulated PD-L1/L2 expression on macrophages as compared to non-stimulated cells. The results demonstrated that the ability of S. epidermidis SCVs to induce elevated levels of anti-inflammatory cytokine, IL-10, and reduced transcriptional induction of TNF-α, together with expression of PD-L1 on macrophages and the ability to persist intracellularly without damaging the host cell could be the key factor contributing to chronicity of SCV infections.
authors.affiliation: Chair and Department of Medical Microbiology, Medical University of Lublin, ul. Chodźki 1, 20-093, Lublin, Poland, agnieszka.magrys@umlub.pl.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Magryś
authors.forename: Jolanta
authors.initials: J
authors.lastname: Paluch-Oleś
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Bogut
authors.forename: Michał
authors.initials: M
authors.lastname: Kiełbus
authors.forename: Dorota
authors.initials: D
authors.lastname: Plewik
authors.forename: Maria
authors.initials: M
authors.lastname: Kozioł-Montewka
mesh_terms: D060890:B7-H1 Antigen / Q000096:biosynthesis*; D001672:Biocompatible Materials / Q000009:adverse effects*; D002460:Cell Line; D004866:Equipment Contamination; D006801:Humans; D016753:Interleukin-10 / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism / Q000382:microbiology; D010446:Peptide Fragments / Q000235:genetics; D061027:Programmed Cell Death 1 Ligand 2 Protein / Q000096:biosynthesis*; D013203:Staphylococcal Infections / Q000209:etiology* / Q000276:immunology; D013212:Staphylococcus epidermidis; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
chemical_list: D060890:B7-H1 Antigen; D001672:Biocompatible Materials; C508609:IL10 protein, human; D010446:Peptide Fragments; D061027:Programmed Cell Death 1 Ligand 2 Protein; C439524:TNF protein, human; D014409:Tumor Necrosis Factor-alpha; C076419:tumor necrosis factor (1-26); D016753:Interleukin-10