CD56 Is a Pathogen Recognition Receptor on Human Natural Killer Cells
Sabrina Ziegler1, Esther Weiss1, Anna-Lena Schmitt1
1Department of Internal Medicine II, WÜ4i, University Hospital Wuerzburg, Wuerzburg, Germany.
Abstract:
Aspergillus (A.) fumigatus is an opportunistic fungal mold inducing invasive aspergillosis (IA) in immunocompromised patients. Although antifungal activity of human natural killer (NK) cells was shown in previous studies, the underlying cellular mechanisms and pathogen recognition receptors (PRRs) are still unknown. Using flow cytometry we were able to show that the fluorescence positivity of the surface receptor CD56 significantly decreased upon fungal contact. To visualize the interaction site of NK cells and A. fumigatus we used SEM, CLSM and dSTORM techniques, which clearly demonstrated that NK cells directly interact with A. fumigatus via CD56 and that CD56 is re-organized and accumulated at this interaction site time-dependently. The inhibition of the cytoskeleton showed that the receptor re-organization was an active process dependent on actin re-arrangements. Furthermore, we could show that CD56 plays a role in the fungus mediated NK cell activation, since blocking of CD56 surface receptor reduced fungal mediated NK cell activation and reduced cytokine secretion. These results confirmed the direct interaction of NK cells and A. fumigatus, leading to the conclusion that CD56 is a pathogen recognition receptor. These findings give new insights into the functional role of CD56 in the pathogen recognition during the innate immune response.
Insights
Human natural killer (NK) cells combat Aspergillus (A.) fumigatus by directly interacting via the CD56 receptor. This interaction is crucial for NK cell activation and cytokine release, identifying CD56 as a key pathogen recognition receptor.
Area of Science:
- Immunology
- Mycology
- Cell Biology
Background:
- Invasive aspergillosis (IA) poses a threat to immunocompromised patients.
- The mechanisms of antifungal activity by human natural killer (NK) cells are not fully understood.
- Pathogen recognition receptors (PRRs) involved in NK cell response to fungi remain largely unidentified.
Purpose of the Study:
- To investigate the cellular mechanisms and pathogen recognition receptors involved in NK cell interactions with Aspergillus (A.) fumigatus.
- To elucidate the role of the CD56 surface receptor in NK cell-mediated antifungal immunity.
Main Methods:
- Flow cytometry to analyze CD56 expression on NK cells.
- Scanning Electron Microscopy (SEM), Confocal Laser Scanning Microscopy (CLSM), and direct Stochastic Optical Reconstruction Microscopy (dSTORM) to visualize NK cell-fungal interactions.
- Cytoskeleton inhibition assays to assess the active nature of receptor reorganization.
- Blocking of CD56 to evaluate its role in NK cell activation and cytokine production.
Main Results:
- CD56 expression on NK cells decreased upon contact with A. fumigatus.
- NK cells directly interact with A. fumigatus, with CD56 accumulating at the interaction site in a time-dependent manner.
- CD56 reorganization is an active process dependent on actin cytoskeleton rearrangements.
- Blocking CD56 reduced fungal-mediated NK cell activation and cytokine secretion.
Conclusions:
- CD56 is directly involved in the interaction between NK cells and A. fumigatus.
- CD56 functions as a pathogen recognition receptor (PRR) in the context of fungal infection.
- These findings provide novel insights into the innate immune response against fungal pathogens, highlighting CD56's role in pathogen recognition.
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