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SUMMARY:Of novel MAMPs and DAMPs: Discovery of novel inflammatory pathways
  mediated by innate immunity - Prof Alex Weber\, University of Tübingen\,
  Germany. Hosted by Prof Felix Randow
DTSTART:20220905T130000Z
DTEND:20220905T140000Z
UID:TALK177557@talks.cam.ac.uk
CONTACT:Nadine Hirst
DESCRIPTION:Innate Immunity employs so-called pattern recognition receptor
 s (PRRs) for initiating inflammation as a step towards resolving both infe
 ctious and sterile insults. These pathways are triggered by microbe-associ
 ated (MAMPs) or danger-associated (DAMPs) molecular patterns\, respectivel
 y. We recently discovered two novel MAMP and DAMP pathways. Firstly\, we f
 ound the secreted host enzyme\, CHIT1\, to convert the inert polymeric MAM
 P and fungal cell wall/allergen component\, chitin\, into diffusible chiti
 n oligomers that can be sensed by TLR1-TLR2 co-receptor/receptor heterodim
 ers\, a process promoted by lipopolysaccharide binding protein (LBP) and C
 D14. Our study shows the existence of an inducible system of MAMP generati
 on within the human host that enables contact-independent immune activatio
 n by diffusible MAMP ligands with striking similarity to the plant kingdom
 . Secondly\, we identified naRNA (NET-associated RNA)\, as a new canonical
  component of neutrophil extracellular traps (NETs) and a potent disease-e
 xacerbating novel DAMP. naRNA\, in complex with the host antimicrobial pep
 tide LL37\, propagated a self-amplifying cycle of NET formation in naïve 
 neutrophils\, dependent on TLR8 in humans and Tlr13 in mice\, in vitro and
  in vivo. Our data not only highlight naRNA as a novel DAMP driving immune
  activation\; naRNA also provides a molecular link between the reported re
 spective pathophysiological roles of NETs and extracellular RNA in multipl
 e diseases\, and suggest blockade of TLR-mediated RNA sensing as a potenti
 al new interventional target.
LOCATION:Sanger Seminar Room\, Level 3\, LMB
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