Broz Lab

Congratulations to Jakub who led this project and all authors for their contributions!

Finally, we show that increased membrane curvature makes more sites for caspase4 to bind, which we observe with immunogold/TEM and MD simulations, thanks to key contributions from @masarykuniversity.bsky.social

Fragmentation of these membranes increases caspase-4 binding to LPS, and its caspase activity, which is an essential part of inflammasome activation.

With key contributions from @leonieanton.bsky.social performing cryo-CLEM, we were able to visualize deformation of Salmonella membranes on GBP1 coated cytosolic Salmonella, but not vacuolar Salmonella.

We highlight the key role of GBP1 as a mechanoenzyme, capable of fragmenting LPS in vitro, dependent on the GTP (check out those mini micelles in the TEM on the bottom right!).

Caspase-4 binds to LPS membranes with positive curvature for non-canonical inflammasome activation The non-canonical inflammasome, comprising caspase-4 in humans, initiates pyroptosis upon sensing cytosolic lipopolysaccharide (LPS) from Gram-negativ…

We're thrilled to share the lab's latest publication demonstrating how caspase-4 and the non canonical inflammasome recognize cytosolic LPS by preferentially binding to the convex portions of membranes - both bacterial and micelles @cp-immunity.bsky.social
www.sciencedirect.com/science/arti...

Join us for the upcoming innate immunity keystone. There’s a great lineup of speakers.
@keystoneSymposia.bsky.social #InnateImmunity : Diversity in #HostDefense & Disease, this March!
keysym.us/KSInnateImmune26 #KSInnateImmune26

Congratulations to (former!) postdoc @ehartenian.bsky.social on launching her career with a prestigious @snf-fns.ch Ambizione grant at the @dib-unil.bsky.social studying how hosts respond to viral infection in her own lab here at the @dib-unil.bsky.social!

Trois récipiendaires Ambizione rejoignent la FBM Cette année, trois jeunes scientifiques viennent renforcer la Faculté de biologie et de médecine (FBM) de l’Unil. Lauréat·es des subsides Ambizione du Fonds national suisse, Ella Hartenian, David Robe...

Congratulations and welcome to Ella Hartenian @ehartenian.bsky.social, who will be launching her group in our Department of Immunobiology in 2026!

www.unil.ch/news/fr/1764...

Join us for an all-star line up for the 2026 #KeystoneSymposia on #InnateImmunity, co-organised by @jkagan1.bsky.social & @brozlab.bsky.social A joint meeting with joint meeting with the Keystone Aging Symposium in beautiful Banff, Canada. Register now! #inflammasomes, #TLRs, #myeloid, #epithelia

The NLRP6 #inflammasome is activated by sterile or pathogen-induced endolysosomal damage
Petr Broz @brozlab.bsky.social and colleagues
www.embopress.org/doi/full/10....

The week of publications continues for the lab with a @currentbiology.bsky.social piece on ninj1 by @elliottbernard.bsky.social and @ehartenian.bsky.social check it out to have all your pressing ninj1 questions answered :)

www.cell.com/current-biol...

Annndddd it’s out! Here’s what came out of combining my virology background with the @brozlab.bsky.social’s cell death focus : a novel role for the cell death protein ninj1 during hsv1 infection. In brief, Ninj1 on mouse macrophages results in lower infection rates and higher cytokine secretion.

You (bacteria) shall not pass: NLRP6 can sense you! - The EMBO Journal The EMBO Journal - The ability of intracellular bacteria to spread directly from one cell to the next, avoiding extracellular immune defenses and drugs, is essential for pathogen dissemination and,...

Thanks to authors of the News&Views for highlighting the role of NLRP6 in sensing homeostatic disruption
@alexandraboegli.bsky.social @embojournal.org

link.springer.com/article/10.1...

The NLRP6 inflammasome is activated by sterile or pathogen-induced endolysosomal damage - The EMBO Journal The cytosolic innate immune sensor NLRP6 controls host defense against bacteria and viruses in the gastrointestinal tract, but the underlying mechanism is poorly understood. Here, we report that NLRP6...

link.springer.com/article/10.1...

NINJ1 blocks HSV-1 entry into macrophages to impact viral replication and immunity | EMBO reports imageimageNINJ1 blocks HSV-1 entry into mouse macrophages independent of its role in cell death, resulting in greater secretion of pro inflammatory cytokines downstream of infection. Mouse macrophages lacking NINJ1 are more permissive to HSV-1 ...

November is a big month for the lab with *two* new papers by @ehartenian.bsky.social and @alexandraboegli.bsky.social ++ co authors now online.

www.embopress.org/doi/full/10....

It’s DIB day! The annual conference for our department @dib-unil.bsky.social. Lovely day (and view!) at the Lausanne Olympic museum exchanging with our colleagues. Plus a stellar presentation on NINJ1 by our own @elliottbernard.bsky.social 🔬!

The second day of the @dib-unil.bsky.social #PRR symposium kicks off with more excellent talks including our own Jakub Began.

Kicking off the 2nd Symposium on the Immunobiology of Pattern Recognition Receptors organized by our department in Lausanne!

@brozlab.bsky.social @martinon.bsky.social @rebsamenlab.bsky.social @fbm-unil.bsky.social

Full room at the start of the 2nd Immunobiology symposium on pattern recognition receptors!
Looking forward to the great programme that we lined up for you together with @brozlab.bsky.social @martinon.bsky.social

#ImmunoSky

Are you an excellent researcher in the field of genomics of infectious diseases of intracellular pathogens (viruses, intracellular parasites or bacteria)? The apply for this chair of excellence at the University of Geneva, Faculty of Medicine:
jobs.unige.ch/www/wd_porta...

Cardiolipin inhibits the non-canonical inflammasome by preventing LPS binding to caspase-4/11 | The EMBO Journal imageimageAvailable caspase-4/11 (CASP4/11) inhibitors also block the activity of caspase-1 (CASP1), which complicates interpretation of results in functional studies and limits their clinical potenti...

Congrats to @malvinapiz.bsky.social and @inflammasomelab.bsky.social on their new paper on the role of cardiolipin in non canonical inflammasome activation. We’re happy to have contributed to the story 🎉🦠!!

www.embopress.org/doi/full/10....

Molecular mechanisms of co-infections | EMBO reports EMBO Press is an editorially independent publishing platform for the development of EMBO scientific publications.

Here is the latest review from the lab on co infections 🥳. Following up on Philipp’s previous work, Philipp and Petr address what is known and all the open questions in this field :

www.embopress.org/doi/full/10....

A big congratulations to Dr. Alexandra Boegli for very successfully defending her PhD on listeria activation of the elusive NLRP6! Very well deserved and very well celebrated! 🥳

Registration opens soon for the second Pattern Recognition receptor symposium in Lausanne Switzerland in October 2025. Check out the link for the great list of speakers.

wp.unil.ch/immunobiolog...

Congrats to lab member Elliott for winning the poster prize at the Swiss LS2 conference for his work on the activation mechanism of Ninj1 during cell death!! 🥳 @dib-unil.bsky.social @lifesciswitzerland.bsky.social

So, NLRP6 can initiate a canonical inflammasome and induces pyroptosis, establishing NLRP6 as a sensor for damage to the endolysosomal system.

Finally, sterile endolysosomal damage alone, using the lysosome rupturing compound LLOME, is sufficient to activate NLRP6.

On the bacterial side, bacterial PAMPs aren’t sufficient to activate NLRP6. However, cell to cell spread is important for activation as a mutant deficient for making actin tails is a worse activator of NLRP, as is the plcB mutant deficient in escape from a secondary vacuole.

By comparing NLRP6 and 3, they map the upstream region of the NACHT domain - the FISNA and its conserved poly basic motifs- as being important for receptor activation, but despite sequence similarities they show that each receptor is activated by distinct ligands.