Clinical Staphylococcus aureus inhibits human T-cell activity through interaction with the PD-1 receptor
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Staphylococcus aureus (S. aureus) represents a major clinical challenge due to its explicit capacity to select mutations that increase antibiotic resistance and immune evasion. However, the molecular mechanisms are poorly defined, especially for adaptive immunity. Cancer immunotherapy targeting programmed cell death protein 1 (PD-1) enhances T-cell activity and is emerging for the treatment of certain viral infections, while its potential against bacterial infections remains elusive. We show that an S. aureus clpP mutant, selected during clinical antibiotic therapy, inhibits T-cell activity by directly interacting with PD-1 on human T cells. Specificity of the interaction was confirmed using recombinant PD-1, as well as PD-1 overexpressing and knock out cells. Moreover, the PD-1-binding S. aureus inhibited intracellular calcium mobilization, T-cell proliferation, CD25 expression, and IL-2 secretion, while the key effects were alleviated by antibody-mediated PD-1 blockade using an engineered IgG1-based anti-PD-1 antibody. Our results suggest that clpP mutant S. aureus directly targets PD-1 to evade immune activation and that therapeutic targeting of PD-1 may be used against certain staphylococcal infections.
Original language | English |
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Article number | e01349-23 |
Journal | mBio |
Volume | 14 |
Issue number | 5 |
Number of pages | 21 |
ISSN | 2161-2129 |
DOIs | |
Publication status | Published - 2023 |
Bibliographical note
Publisher Copyright:
Copyright © 2023 Mellergaard et al.
- adaptive immunity, clinical Staphylococcus aureus, ClpP mutation, immune evasion, T cells
Research areas
ID: 383443871