The innate immune sensor Toll-like receptor 2 controls the senescence-associated secretory phenotype

Priya Hari, Fraser R. Millar, Nuria Tarrats, Jodie Birch, Andrea Quintanilla, Curtis J. Rink, Irene Fernández-Duran, Morwenna Muir, Andrew J. Finch, Valerie G. Brunton, João F. Passos, Jennifer P. Morton, Luke Boulter, Juan Carlos Acosta

Research output: Contribution to journalArticlepeer-review

30 Scopus citations

Abstract

Cellular senescence is a stress response program characterized by a robust cell cycle arrest and the induction of a proinflammatory senescence-associated secretory phenotype (SASP) that is triggered through an unknown mechanism. Here, we show that, during oncogene-induced senescence (OIS), the Toll-like receptor 2 (TLR2) and its partner TLR10 are key mediators of senescence in vitro and in murine models. TLR2 promotes cell cycle arrest by regulating the tumor suppressors p53-p21CIP1, p16INK4a, and p15INK4b and regulates the SASP through the induction of the acute-phase serum amyloids A1 and A2 (A-SAAs) that, in turn, function as the damage-associated molecular patterns (DAMPs) signaling through TLR2 in OIS. Last, we found evidence that the cGAS-STING cytosolic DNA sensing pathway primes TLR2 and A-SAAs expression in OIS. In summary, we report that innate immune sensing of senescence-associated DAMPs by TLR2 controls the SASP and reinforces the cell cycle arrest program in OIS.

Original languageEnglish (US)
Article numberaaw0254
JournalScience Advances
Volume5
Issue number6
DOIs
StatePublished - Jun 5 2019

ASJC Scopus subject areas

  • General

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