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

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
Article numbereaaw0254
Number of pages14
JournalScience Advances
Volume5
Issue number6
DOIs
Publication statusPublished - 5 Jun 2019

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