TLR agonists enhance responsiveness of inflammatory innate immune cells in HLA-B*57-positive HIV patients
| Autor: | Leona Dold, K. Ommer, Benjamin Krämer, Christoph Boesecke, J. K. Rockstroh, L. Zimmer, Jacob Nattermann, C. Schwarze-Zander, Bettina Langhans, Christian P. Strassburg, J. C. Wasmuth, B. Gathof, Ulrich Spengler, Raphael Mohr |
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| Rok vydání: | 2020 |
| Předmět: |
Lipopolysaccharides
Male T-Lymphocytes HIV Infections Monocytes 0302 clinical medicine Bacterial infections Drug Discovery Cytotoxic T cell 030212 general & internal medicine Genetics (clinical) Host factor Aged 80 and over 0303 health sciences Toll-Like Receptors Middle Aged Killer Cells Natural medicine.anatomical_structure Oligodeoxyribonucleotides Cytokines Molecular Medicine Female Original Article Inflammatory immune response Adult HLA-B*57 CD14 T cell cART CD16 Sepsis Lipopeptides Young Adult 03 medical and health sciences medicine Humans Aged 030304 developmental biology Inflammation Innate immune system business.industry Monocyte HIV medicine.disease Immunity Innate Toll-like receptor stimulation HLA-B Antigens Toll-Like Receptor 9 Immunology business |
| Zdroj: | Journal of Molecular Medicine (Berlin, Germany) |
| ISSN: | 1432-1440 0946-2716 |
| Popis: | Abstract HLA-B*57 affects the course of HIV infection. Under antiretroviral therapy, its effects cannot be explained by outstandingly efficient T cell responses alone but may also involve cells of innate immunity. Studying in vitro stimulation with Pam3CSK4, E. coli LPS-B5 and CpG-ODN-2216, we observed greater induction of IL-6/IL-1beta double-positive CD14+CD16++ monocytes as well as IFN-gamma-positive cytotoxic CD56highCD16neg NK cells in HLA-B*57- versus HLA-B*44-positive HIV patients, while TNF-alpha induction remained unchanged. Differences were not seen in the other monocyte and NK cell subsets or in HLA-matched healthy controls. Our findings show that, in virally suppressed HIV infection, HLA-B*57 is associated with enhanced responsiveness of inflammatory innate immune cells to TLR ligands, possibly contributing to increased vulnerability in sepsis. Key messages • HLA-B*57 is a host factor affecting clinical outcomes of HIV infection. • HLA-B*57 modifies inflammatory subsets of NK cells and monocytes in HIV infection. • In HLA-B*57-positive HIV patients TLR agonists induce enhanced IL-6/IL-1beta in monocytes. • NK cells from HLA-B*57 HIV patients release more IFN-gamma upon TLR costimulation. • HLA-B*57 is linked to enhanced inflammatory responsiveness to TLR ligands. |
| Databáze: | OpenAIRE |
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