The role of programmed death ligand 1 pathway in persistent biomaterial-associated infections

Agnieszka Magrys; Jolanta Paluch-Oles; Agnieszka Bogut; Michal Kielbus; Dorota Plewik; Maria Koziol-Montewka

doi:10.1007/s12275-015-5022-7

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The role of programmed death ligand 1 pathway in persistent biomaterial-associated infections: Agnieszka Magrys ¹, Jolanta Paluch-Oles ¹, Agnieszka Bogut ¹, Michal Kielbus ², Dorota Plewik ³, Maria Koziol-Montewka ¹; Journal of Microbiology 2015;53(8):544-552.
DOI: https://doi.org/10.1007/s12275-015-5022-7
Published online: July 31, 2015

¹Chair and Department of Medical Microbiology, Medical University of Lublin, ul. Chodzki 1, 20-093 Lublin, Poland, ²Chair and Department of Biochemistry and Molecular Biology, Medical University of Lublin, ul. Chodzki 1, 20-093 Lublin, Poland, ³Research Centre for Innovation, Pope John Paul II State School of Higher Education in Biala Podlaska, ul. Sidorska 105, 21-500 Biala Podlaska, Poland

Corresponding author: Agnieszka Magrys , Tel: +48-81-742-37-81,

Received: 13 January 2015 • Revised: 17 June 2015 • Accepted: 17 June 2015

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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.

Keywords: PD-L1;Staphylococcus epidermidis;small colony variants;biomaterial-associated infections

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The role of programmed death ligand 1 pathway in persistent biomaterial-associated infections

J. Microbiol. 2015;53(8):544-552. Published online July 31, 2015

DOI: https://doi.org/10.1007/s12275-015-5022-7

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