Dendritic cells Trigger IFN-γ secretion by NK cells independent of IL-12 and IL-18.
Eur J Immunol
; 52(9): 1431-1440, 2022 09.
Article
em En
| MEDLINE
| ID: mdl-35816444
ABSTRACT
It is commonly believed that IL-12 produced by DCs in response to pathogens is the first signal that stimulates the production of IFN-γ by NK cells. However, IL-12 production by DCs in response to bacterial LPS depends on either engagement of CD40 by CD40L on activated T cells or IFN-γ from NK cells. This suggests that during the primary immune response, NK cells produce IFN-γ before IL-12 production by DCs. Here, using single-cell measurements, cell sorting and mouse lines deficient in IL-12, IL-23, type I IFN receptor and the IL-18 receptor, we show that a subset of BM-derived DCs characterized by low expression of MHC class II (MHCIIlow ) stimulates IFN-γ production by NK cells. The expression of Toll-like Receptor (TLR) 4 on DCs but not NK cells was required for such NK-derived IFN-γ. In addition, soluble factor(s) produced by LPS-activated MHCIIlow DCs were sufficient to induce IFN-γ production by NK cells independent of IL-12, IL-23, and IL-18. This response was enhanced in the presence of a low dose of IL-2. These results delineate a previously unknown pathway of DC-mediated IFN-γ production by NK cells, which is independent of commonly known cytokines.
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Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Interleucina-12
/
Interleucina-18
Limite:
Animals
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article