Have you ever wondered whether pyroptotic corpses have functions beyond the grave? We made the surprising discovery that pyroptotic corpses are flagged by #filopodia to alert #DendriticCells they need autopsy. A short Tweetorial (1/13)👇with movies! Link:

Announcing, one of a unique conference. #CellDeath, #Innateimmunity, and #Autophagy. Top speakers, top Science. website -open soon- Please retweet. @EMBO @India_Alliance @ccmb_csir @CSIR_IND @jkagan1 @dixitvishva @vpderetic @v_hornung @ThiruKanneganti @ClareBryant13 @iDikic2

This allowed us to ask cool new questions (🧵3/3): -are inflammasomes activated & deactivated in steady-state? -is inflammasome silencing critical to prevent disease? -after a major organ challenge, is it critical to silence inflammasomes to restore homeostasis? 👀📰 for answers!

We previously discovered that an unusual mechanism of feedback inhibition turns off #inflammasomes in cells (2018 J Exp Med). Our new mouse model confirms this also terminates #inflammasomes in vivo (🧵2/3) https://t.co/matX4dWzXp https://t.co/SjqRy7QuNS

Inflammatory signalling must eventually be turned off (e.g. by feedback inhibition) to prevent chronic inflammation. We didn't know how #inflammasomes turn off their signalling in vivo ... until now! (🧵: 1/3) https://t.co/lSaEhso0lw

Sad to leave what used to be a fun community on Twitter, but I am joining the X-odus! Please find me at my preferred academic social network on @inflammasomelab.bsky.social 😀

Thrilled to start 2025 with our latest findings! @fallfelfallen Yersinia invades macrophage cytosol to activate caspase-11 when caspase-8 or YopJ are inactive

So excited to have this paper out now! Pyroptotic EVs “transplant” gasdermin pores from dying cells onto bystander cells, propagating pyroptosis and inflammation. https://t.co/XgU6jt15aF @uconnresearch @uconnhealth 1/3

Now online - research briefing from @inflammasomelab Mercedes Monteleone on our recent @NatImmunol publication on how pyroptotic cell corpses signal to dendritic cells from beyond the grave! #inflammasomes #pyroptosis @IMBatUQ @UQ_News @arc_gov_au Link:

Join us on December 16 for the final Inflammazoom webinar of 2024, featuring talks on from Kate Shroder @inflammasomelab @UQ_News and @SiMingMan1 @ourANU 🔬🎤 Register here to access the live session as well as on-demand talks from past sessions: https://t.co/aGA7yfavN3

📢 Excited to see our Luminary, Prof James Murphy @pseudokinase as a newly appointed deputy director of @WEHI_research in 2025! His visionary leadership will shape the future of WEHI and continue to inspire the next generation of scientists🔬🚀 Read more:

Inflammazoom on Monday (early in the West) with the incomparable Si Ming Man and Kate Schroder: catch up on line if you miss it

Abstract submission for the #NCII2025 innate immunity #conference is open! If you are interested in #immunology topics like #inflammasome, #neutrophil, #innate_immunity in skin, brain or #cancer, #microbiome, and more 👉check https://t.co/JBDzwEAiJ7

Imagine cells bursting into tiny fireworks to alert the immune system and spark a powerful defense. @CarolineLHolley @inflammasomelab @jkagan1 @AriottiNick @SamStehbens @s_burgener @DoktrNick @UQ_News @ASImmunology @IMBatUQ @AusCellDeathSoc @arc_gov_au https://t.co/dE9wPARavh

Huge thanks to @arc_gov_au @nhmrc @UQ_News for funding, & many labs for wonderful collaborations (@SamStehbens @jkagan1 @DoktrNick @DrNickCondon @LahoudMirei @AriottiNick Yap), & the whole @inflammasomelab team for contributing (13/13). @ASImmunology @IMBatUQ @AusCellDeathSoc

Summary: pyroptotic & necroptotic cells assemble filopodia to ⛳️ their corpses. These flag pyroptotic corpses for recognition by #DCs, via the corpse antigen sampling receptor, #CLEC9A. Does this trigger Ag-specific immunity in #infection, #vaccination & #autoimmunity? 🤯 (12/13)

In clever expts by @s_burgener, DCs reacted to the calcium-sensitive filopodia of corpses by phosphorylating SYK via #CLEC9A. While #NINJ1-driven #CellExplosion was not needed for filopodial assembly (L; M. Monteleone), it was required to expose F-actin to #CLEC9A🤯. #PMR (11/13)

Why do #pyroptotic cells use their final minutes to make #filopodia? Well, #filopodia are rich stores of F-actin under the plasma membrane. Could #CellExplosion during #pyroptosis reveal filopodial F-actin to engage the corpse antigen sampling DC receptor, #CLEC9A/#DNGR1? (10/13)

The killer question: are pyroptotic corpses immunogenic to incoming #DendriticCells? Joon Choi & @jkagan1 tested this 🙏, finding that DCs ⬆️MHCII & costimulus in response to corpses, if the latter had Ca2+ to make filopodia. These DCs are preparing to present antigen! (9/13)

#HighRes imaging revealed the spectacular morphology of #pyroptosis, with clustered pyroptotic blisters (L, blue) causing asymmetric #CellRupture that blows out a portion of the cell, like a popped balloon (R, SEM by @AriottiNick). Filopodia remain, crowning the corpse 👑 (8/13)

Filopodial projections crowed #pyroptotic & #necroptotic corpses, but were absent from #apoptotic corpses - even when apoptosis was triggered by #inflammasome signalling in GSDMD-null cells. So filopodia = a flag that a cell lysed 'under suspicious circumstances' ⛳️ (7/13)