Thank you very much for highlighting our work. This is one of our first big stories coming from out the lab, so we are very excited!

Thanks again @alinabatzi.bsky.social for a titanic work, and all the lab. @jamesasharpe.bsky.social lab and Lars Steinmetz lab for computational help. Miguel and Mireia at UPF for insights in immune-endothelial responses, and my ❤️ friend @moncunill.bsky.social, for getting us into deep immuno!

Our study shows the power of using bioengineered models in combination with deep single cell profiling to study complex immune responses.

For the first time, we can introduce different infection relevant drivers into human models to identify their individual role in tissue damage.

Alina finally integrated the scRNAseq immune dataset with our recently published dataset of the 3D-BBB model being exposed to P. falciparum. We identified shared and dominant disrupted pathways (JAK-STAT!) in all cells. As well as parasite/immune-specific disruptive pathways on endothelial cells.

Barrier disruption was mostly mediated by locally acting granzyme B and IFNy secreted by gd T cells and NK cells. We could prevent barrier disruption by preventing immune cell binding with anti-ICAM-1 antibodies.

More important, P. falciparum-stimulated immune cells cause BBB disruption, making the barrier leakier through decrease junctional VE-cadherin, increase contractility and apoptosis

Monocytes, gd T cells and NK cells cells secrete TNFa and IFNg, causing a strong inflammation and activation of all BBB cells, accounting for 20% of changes in the transcriptome.

In a project spearheaded by the relentless @alinabatzi.bsky.social, we used an immunocompetent 3D-Blood brain barrier (BBB) model and found that Plasmodium falciparum stimulated immune cells accumulate much more to the BBB (mostly T-cells), driven by changes on LFA high-affinity conformation

I think I didn't 🙈 but @rorykmlong.bsky.social left everything ready, so there was a very minimum chance for me to screw up! ☺️

This article highlights the importance of agressive antypiretic treatment in malaria infections and has potential consequences for other infections and brain injuries!!!!

We could reverse this highly negative effect by protecting the endothelial glycocalyx with Batimastat, an MMP1 inhibitor.

This effect was conserved in lung 3D microvessels, as well as an increase in neutrophil binding.

Just a short 30 min exposure to 40C, common in malaria patients, significantly increased parasite binding to 3D microvessels at multiple flow conditions. We found this occurred in several parasite lines with tropism in the brain, without apparent changes in their endothelial receptors EPCR and ICAM

It has been amazing that you were my (co-)first PhD student. Amazing journey. You should be proud of everything you achieved

A big thanks to everyone, who contributed to the project.To the full Bernabeu group, as this was a team project! As well as our @embl.org collaborators @jamesasharpe.bsky.social group, @yschwab.bsky.social's team and Lars Steinmetz group!

More important, we could reverse the increase in vascular barrier permeability induced by malaria products with Ruxolitinib, a JAK-STAT inhibitor! This is super exciting with the drug now being tested in CHMI studies. www.medrxiv.org/content/10.1...

We also found that falciparum egress products activate interferon and antigen presenting pathways in all the cells that compose the BBB, endothelial, astrocytes and pericytes. Including JAK-STAT as one of the key signaling inflammatory hubs