Caspase-4 is also recruited to these structures in a GBP1-dependent manner, independently of LPS!

GBP1 is recruited to sites of 'sterile' actin-rich structures produced by FcgR-Tir chimera independently of LPS!

We made an FcgR-Tir chimera, i.e., Fcg-Receptor extracellular domain + intracellular signalling domain of Tir, and activated it by crosslinking with IgG-coated polystyrene beads. This produces 'sterile' actin-rich structures independently of bacteria, other T3SS-effectors & LPS!

How does GBP1 sense these extracellular bacteria? Using a range of EPEC and EHEC mutants, we show that pathogen-induce actin polymerisation is essential for GBP1 recruitment, pyroptosis and IL-18 release (a substrate of human caspase-4).

Guess what, GBP1 recruits caspase-4 to EPEC/EHEC pedestals for pyroptosis. This clarifies the role of caspase-4 that we previously showed in pyroptosis caused by these pathogens. (pubmed.ncbi.nlm.nih.gov/31018119/; pubmed.ncbi.nlm.nih.gov/33378358/).

GBP1 is also recruited to actin pedestals of EHEC in epithelial cells and C. rodentium-infected colonocytes in vivo in mice.

We show that GBP1 is recruited to actin-rich pedestals of EPEC. The T3SS mutant strain (escF) cannot manipulate actin, recruit GBP1 or trigger pyroptosis. Importantly, GBP1 is recruited to pedestals of various EPEC strains independently of the type of their LPS O-antigens.

EPEC/EHEC and the mouse pathogen C. rodentium (CR) attach tightly to cells and manipuate the host actin cytosokeleton by forming actin-rich 'pedestals'. This requires the T3SS-effector Tir (translocated intimin receptor) binding to Intimin (an adhesin on bacterial surface).

We've worked on extracellular Gram-negative pathogenic E. coli (EPEC & EHEC) for several years. EPEC is a major cause of childhood diarrhoeas and EHEC can be fatal even in adults. Here we show that GBP1 is required for EPEC/EHEC-induced pyroptosis in non-phagocytic cells.

📢A new effector-triggered immunity role for GBP1! No place for pathogens to hide now that GBP1 can detect extracellular pathogens that hijack the actin cytoskeleton. Surprise*suprise* GBP1 does this independently of LPS! 🧵
biorxiv.org/content/10.1...

📢 paper - a new class of RIPK1 inhibitors. Lots of with here, with structure of it bound to RIPK1, biochemistry and more! Was fun being part of this with Tate group and many others.
pubs.acs.org/doi/10.1021/...

Interesting talks today on sustainability in education in the Festival of Learning and Teaching @imperialinfect.bsky.social

📢 I'll be hosting Jack Aunty & Kesavardana Sannula in the next InflammaZoom seminar series on Monday 20th Jan at 8am GMT, 1:30pm IST, 7pm AEDT. Register here:
@keshu-vrimmch.bsky.social

events.abcam.com/event/Inflam...

This month we welcomed our newest PhD student, Ayush Punwatkar, who is funded by the National Overseas Scholarship from the Govt of India. He's going to work on, what else, inflammasomes 😉

Last week we welcomed Dharitri Chaudhuri, a PhD student from Sandhya's lab at IISc Bangalore. During her placement, she will work on a major problem in countries like India: EPEC infections & diarrhoeal disease. Thanks to funding from the Commonwealth Scholarships cscuk.fcdo.gov.uk/scholarships...