Macrophages on soft, tissue-like surfaces switch on the NLRP3 inflammasome in response to LPS alone. Matrix stiffness controls this behaviour through the transcription factor NRF2, acting as a transcriptional checkpoint for inflammasome activity.
We show that TRAM promotes the release of nascent myddosomes from plasma membrane TLR:TIRAP complexes. The resulting receptor-free cytosolic myddosomes sustain MyD88-dependent signal transduction on their own.
Cells dying by pyroptosis grow F-actin-rich filopodia that remain on the corpse after cell lysis. Dendritic cells detect these filopodia through CLEC9A, linking inflammasome activation to adaptive immunity.
We redefined how signaling by activated Toll-like receptors is computed by myddosomes in human and mouse macrophages. Myddosomes interact only briefly with the receptors, change in size and composition over a day, and execute the entire TLR pathway from within.
We discovered a guard mechanism in human cells that monitors the integrity of IFNγ signaling: the kinase PIM1 phosphorylates GBP1 and keeps it inactive. Because IFNγ induces both proteins, pathogens that suppress IFNγ signaling deplete PIM1 and release GBP1.
p97/VCP and its partners ANKRD13A and UBXD1 target ubiquitinated Toxoplasma vacuoles within two hours of infection and drive their acidification. p97/VCP emerges as a universal IFNγ-dependent restriction factor in human cells.
Human GBPs restrict Toxoplasma in macrophages in two ways. GBP1 acts directly at the parasite vacuole, while other GBPs limit the parasite without targeting it.
HRMAn 2.0 extends our open-source AI image analysis platform to more pathogens and host responses, so labs can quantify complex imaging-based infection phenotypes without writing code.
The Pseudomonas aeruginosa lectin LecA binds the glycolipid Gb3 and gathers CD59 and flotillins into a membrane domain that the bacterium uses to invade lung epithelial cells.
We demonstrate that human GBP1 can break Toxoplasma vacuole membranes and decorates cytosolic Salmonella thereby enabling pattern recognition receptors to detect microbial ligands.
A step-by-step protocol for measuring how host cells and Toxoplasma interact in microscopy images, using our HRMAn pipeline.
A review of detection and control mechanisms against Toxoplasma, from innate sensing and IFNγ to the defenses that individual cells deploy.
C57BL/6 and 129 mice carry different Gbp2 and Gbp2b alleles that respond differently to immune stimuli and infection. Studies using Gbp knockout mice need to account for this background effect.
We describe an LPS-sensing GBP1:caspase-4 signaling platform on the surface of cytosolic Gram-negative bacteria and define a new programmed cell death routine triggered by Toxoplasma gondii.
HRMAn is an open-source machine-learning platform that identifies, classifies and quantifies pathogen killing, replication and host defense in microscopy images.
