SAMHD1 deficient human monocytes autonomously trigger type I interferon

Alicia Martinez-Lopez, Marta Martin-Fernandez, Sofija Buta, Baek Kim, Dusan Bogunovic, Felipe Diaz-Griffero

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Germline mutations in the human SAMHD1 gene cause the development of Aicardi-Goutières Syndrome (AGS), with a dominant feature being increased systemic type I interferon(IFN) production. Here we tested the state of type I IFN induction and response to, in SAMHD1 knockout (KO) human monocytic cells. SAMHD1 KO cells exhibited spontaneous transcription and translation of IFN-β and subsequent interferon-stimulated genes (ISGs) as compared to parental wild-type cells. This elevation of IFN-β and ISGs was abrogated via inhibition of the TBK1-IRF3 pathway in the SAMHD1 KO cells. In agreement, we found that SAMHD1 KO cells present high levels of phosphorylated TBK1 when compared to control cells. Moreover, addition of blocking antibody against type I IFN also reversed elevation of ISGs. These experiments suggested that SAMHD1 KO cells are persistently auto-stimulating the TBK1-IRF3 pathway, leading to an enhanced production of type I IFN and subsequent self-induction of ISGs.

Original languageEnglish (US)
Pages (from-to)450-460
Number of pages11
JournalMolecular Immunology
Volume101
DOIs
StatePublished - Sep 1 2018

Fingerprint

Interferon Type I
Monocytes
Interferons
Genes
Aicardi Syndrome
Blocking Antibodies
Germ-Line Mutation

Keywords

  • AGS
  • IFN
  • ISGs
  • SAMHD1
  • TBK1-IRF3

ASJC Scopus subject areas

  • Immunology
  • Molecular Biology

Cite this

SAMHD1 deficient human monocytes autonomously trigger type I interferon. / Martinez-Lopez, Alicia; Martin-Fernandez, Marta; Buta, Sofija; Kim, Baek; Bogunovic, Dusan; Diaz-Griffero, Felipe.

In: Molecular Immunology, Vol. 101, 01.09.2018, p. 450-460.

Research output: Contribution to journalArticle

Martinez-Lopez, A, Martin-Fernandez, M, Buta, S, Kim, B, Bogunovic, D & Diaz-Griffero, F 2018, 'SAMHD1 deficient human monocytes autonomously trigger type I interferon', Molecular Immunology, vol. 101, pp. 450-460. https://doi.org/10.1016/j.molimm.2018.08.005
Martinez-Lopez, Alicia ; Martin-Fernandez, Marta ; Buta, Sofija ; Kim, Baek ; Bogunovic, Dusan ; Diaz-Griffero, Felipe. / SAMHD1 deficient human monocytes autonomously trigger type I interferon. In: Molecular Immunology. 2018 ; Vol. 101. pp. 450-460.
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