IL-15 cis presentation is required for optimal NK cell activation in lipopolysaccharide-mediated inflammatory conditions.
Natural killer (NK) cells have antitumor, antiviral, and antibacterial functions, and efforts are being made to manipulate them in immunotherapeutic approaches. However, their activation mechanisms remain poorly defined, particularly during bacterial infections. Here, we show that upon lipopolysaccharide or E. coli exposure, dendritic cells (DCs) produce three cytokines-interleukin 2 (IL-2), IL-18, and interferon β (IFN-β)-necessary and sufficient for NK cell activation. IFN-β enhances NK cell activation by inducing IL-15 and IL-15 receptor α not only in DCs but, surprisingly, also in NK cells. This process allows the transfer of IL-15 on NK cell surface and its cis presentation. cis-presented NK cell-derived and trans-presented DC-derived IL-15 contribute equally to optimal NK cell activation.
Department of Biotechnology and Biosciences, University of Milano-Bicocca, Piazza della Scienza 2, 20126 Milan, Italy. Electronic address: ivan.zanoni@unimib.it.
Ivan
I
Zanoni
Roberto
R
Spreafico
Caterina
C
Bodio
Marco
M
Di Gioia
Clara
C
Cigni
Achille
A
Broggi
Tatiana
T
Gorletta
Michele
M
Caccia
Giuseppe
G
Chirico
Laura
L
Sironi
Maddalena
M
Collini
Mario P
MP
Colombo
Natalio
N
Garbi
Francesca
F
Granucci
D000818:Animals; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000276:immunology; D019409:Interleukin-15 / Q000276:immunology* / Q000378:metabolism; D007694:Killer Cells, Natural / Q000166:cytology / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D008070:Lipopolysaccharides / Q000276:immunology / Q000494:pharmacology*; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D015398:Signal Transduction; D013329:Structure-Activity Relationship
D019409:Interleukin-15; D008070:Lipopolysaccharides