Staphylococcus aureus induces cell-surface expression of immune stimulatory NKG2D ligands on human monocytes
| Autor: | Anders Rhod Larsen, Ashleigh S Hayes, Søren Skov, Romain Guérillot, Dorte Frees, Anton Y. Peleg, Benjamin P Howden, Blanca I. Aldana, Sofie Hedlund Møller, Rikke Illum Høgh, Timothy P. Stinear, Stine Dam Jepsen, Lars Andresen, Maiken Mellergaard, Nafsika Panagiotopoulou, Zofija Frimand, Helle S. Waagepetersen, Astrid Lund, Camilla Hartmann Friis Hansen |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Toll-like receptor 030102 biochemistry & molecular biology Phagocytosis Monocyte Immunology chemical and pharmacologic phenomena Cell Biology Biology medicine.disease_cause Staphylococcal infections medicine.disease Biochemistry Microbiology Proinflammatory cytokine 03 medical and health sciences 030104 developmental biology ULBP2 Immune system medicine.anatomical_structure Staphylococcus aureus medicine Molecular Biology |
| Zdroj: | Mellergaard, M, Høgh, R I, Lund, A, Aldana, B I, Guérillot, R, Møller, S H, Hayes, A S, Panagiotopoulou, N, Frimand, Z, Jepsen, S D, Hansen, C H F, Andresen, L, Larsen, A R, Peleg, A Y, Stinear, T P, Howden, B P, Waagepetersen, H S, Frees, D & Skov, S 2020, ' Staphylococcus aureus induces cell-surface expression of immune stimulatory NKG2D ligands on human monocytes ', The Journal of Biological Chemistry, vol. 295, pp. 11803-11821 . https://doi.org/10.1074/jbc.RA120.012673 J Biol Chem |
| ISSN: | 0021-9258 |
| Popis: | Staphylococcus aureus is among the leading causes of bacterial infections worldwide. The pathogenicity and establishment of S. aureus infections are tightly linked to its ability to modulate host immunity. Persistent infections are often associated with mutant staphylococcal strains that have decreased susceptibility to antibiotics; however, little is known about how these mutations influence bacterial interaction with the host immune system. Here, we discovered that clinical S. aureus isolates activate human monocytes, leading to cell-surface expression of immune stimulatory natural killer group 2D (NKG2D) ligands on the monocytes. We found that expression of the NKG2D ligand UL16-binding protein 2 (ULBP2) is associated with bacterial degradability and phagolysosomal activity. Moreover, S. aureus-induced ULBP2 expression was linked to altered host cell metabolism, including increased cytoplasmic (iso)citrate levels, reduced glycolytic flux, and functional mitochondrial activity. Interestingly, we found that the ability of S. aureus to induce ULBP2 and proinflammatory cytokines in human monocytes depends on a functional ClpP protease in S. aureus These findings indicate that S. aureus activates ULBP2 in human monocytes through immunometabolic mechanisms and reveal that clpP inactivation may function as a potential immune evasion mechanism. Our results provide critical insight into the interplay between the host immune system and S. aureus that has evolved under the dual selective pressure of host immune responses and antibiotic treatment. Our discovery of a immune stimulatory pathway consisting of human monocyte-based defense against S. aureus suggests that targeting the NKG2D pathway holds potential for managing persistent staphylococcal infections. |
| Databáze: | OpenAIRE |
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