PS: Thanks to @edelblumlab.bsky.social for showing me how to do a proper Bluetorial (this isn't bad for my first try, right?)

@ukri.org supported this work, which was led by Liya Mathew (funded by Bart's Charity) and is being continued by Sean Carlson with HARP / @wellcometrust.bsky.social. Huge thanks to @chitinette.bsky.social Julian Naglik (KCL) Newman Sze @brocku.ca and of course @eberllab.bsky.social
10/10

What's next? We plan to build even better models of human intestine complete with patient immune cells so we can see how well these defend against fungal attack (and start testing drug treatments that could help prevent this). Got other brilliant ideas? Let us know! 👇 9/10

Could this really happen in the human intestine? To test this, we built a 'mini gut' model complete with fluid flow and tissue stretch, then added in different fungi. C. albicans strains from CD patients were much better at sticking and invading the model tissues like a pathogen might do. 8/10

Do these filaments matter? Well they are pretty BIG so quite difficult for immune cells to eat. In fact, they can even make neutrophils EXPLODE(!) and punch their way out of hungry macrophages 👽. Quite likely bad news for gut inflammation... 7/10

Why was this happening? We found lots of genetic differences between C. albicans strains from healthy donors and CD patients, which also reacted very differently when we put them in low-oxygen conditions similar to the human gut 🫧 6/10

The main type of fungus we isolated from gut biopsies was Candida albicans. Strains from healthy donors looked like harmless oval yeast: 000. Crohn's disease (CD) strains made invasive filaments that we know can break into human tissues: 0------💥  0----💥 5/10

Other labs have shown gut fungi increase in inflammation, so we checked if Vd2+ cells from IBD patients could also pull this trick. Short answer: NO! Vd2+ cells were rare in patient tissue and tough to activate (maybe not helped by some of the treatments used: pubmed.ncbi.nlm.nih.gov/26168223/) 4/10

By total chance, we noticed that activating Vd2+ cells in healthy gut tissue cultures kept them nice and clean, but when we didn't do this they would quickly get overrun by fungus!! 🍄😱 3/10

In previous teamwork with @eberllab.bsky.social, we showed that bacteria-sensing #gdT-cells in human gut tissue (Vdelta2+) are great inducers of IL-22 cytokine and anti-microbial calpro, but why would this be a useful response to make? 🤔 pubmed.ncbi.nlm.nih.gov/28330898/ 2/10