Details

Autor(en) / Beteiligte

• Mourits, Vera P.
• Helder, Leonie S.
• Matzaraki, Vasiliki
• Koeken, Valerie A.C.M.
• Groh, Laszlo
• de Bree, L. Charlotte J.
• Moorlag, Simone J.C.F.M.
• van der Heijden, Charlotte D.C.C.
• Keating, Samuel T.
• van Puffelen, Jelmer H.
• Jaeger, Martin
• Joosten, Leo A.B.
• Netea, Mihai G.

Titel

The role of sirtuin 1 on the induction of trained immunity

Ist Teil von

• Cellular immunology, 2021-08, Vol.366, p.104393-104393, Article 104393

Ort / Verlag

Elsevier Inc

Erscheinungsjahr

2021

Quelle

Access via ScienceDirect (Elsevier)

Beschreibungen/Notizen

• •SIRT1 genetic polymorphisms affect cytokine production of human immune cells upon stimulation.•Inhibition of SIRT1 upregulates pro-inflammatory innate cytokine production upon stimulation.•Trained immunity-induced cytokine production is influenced by SIRT1 genetic polymorphisms.•Modification of SIRT1 in vitro only mildly affects trained immunity-induced cytokine responses. Sirtuin 1 (SIRT1) has been described to modify immune responses by modulation of gene transcription. As transcriptional reprogramming is the molecular substrate of trained immunity, a de facto innate immune memory, we investigated the role of SIRT1 in the induction of trained immunity. We identified various SIRT1 genetic single nucleotide polymorphisms affecting innate and adaptive cytokine production of human peripheral blood mononuclear cells (PBMCs) in response to various stimuli on the one hand, and in vitro induction of trained immunity on the other hand. Furthermore, inhibition of SIRT1 upregulated pro-inflammatory innate cytokine production upon stimulation of PBMCs. However, inhibition of SIRT1 in vitro had no effect on cytokine responses upon induction of trained immunity, while activation of SIRT1 mildly modified trained immunity responses. In conclusion, SIRT1 modifies innate cytokine production by PBMCs in response to various microbes, but has only a secondary role for BCG and β-glucan-induced trained immunity responses.