Cathepsin Z is a conserved susceptibility factor underlying tuberculosis severity Tuberculosis (TB) outcomes vary widely, from asymptomatic infection to mortality, yet most animal models do not recapitulate human phenotypic and genotypic variation. The genetically diverse Collaborative Cross mouse panel models distinct facets of TB disease that occur in humans and allows identification of genomic loci underlying clinical outcomes. We previously mapped a TB susceptibility locus on mouse chromosome 2. Here, we identify cathepsin Z ( Ctsz ) as a lead candidate underlying this TB susceptibility and show that Ctsz ablation leads to increased bacterial burden, CXCL1 overproduction, and decreased survival in mice. Ctsz disturbance within murine macrophages enhances production of CXCL1, a known biomarker of TB severity. From a Ugandan household contact study, we identify significant associations between CTSZ variants and TB disease severity. Finally, we examine patient-derived TB granulomas and report CTSZ localization within granuloma-associated macrophages, placing human CTSZ at the host-pathogen interface. These findings implicate a conserved CTSZ-CXCL1 axis in humans and genetically diverse mice that mediates TB disease severity. ### Competing Interest Statement The authors have declared no competing interest.

New preprint from Clare Smith’s lab on Cathepsin Z as a TB host susceptibility locus - cool collaboration with Hawn and Stein labs @dukemedschool.bsky.social
www.biorxiv.org/content/10.1...

DC bound 🫡 a lot of my colleagues joining there and in Raleigh, NC!! #standupforscience

Funding cuts to tuberculosis programmes endanger millions of lives In the past two decades, tuberculosis (TB) prevention, testing, and treatment services have saved more than 79 million lives—averting approximately 3.65 million deaths last year alone from the world’s...

"Early reports to WHO from the 30 highest TB-burden countries confirm that funding withdrawals are already dismantling essential services, threatening the global fight against TB."

www.who.int/news/item/05...

ATTN #EndTB advocates! Have you seen this new resource assessing the impact associated with the funding freeze & discontinuation on the #TB response? Check it out & make use of it in your awareness raising & #FundTBNow calls to action! Thank you @brookeenichols.bsky.social et al
tb.impactcounter.com

Pittsburgh Stand Up for Science 11-1:30 on March 7, 2025, Schenley Plaza

Yinz ready to stand up for science?

Summary of November reading from StoryGraph. Highest rated books: Remarkably Bright Creatures Consent: a Memoir None of this is True

Busy November meant lots of audiobooks! However, my favorite was a kindle read, and I would highly recommend Remarkably Bright Creatures to anyone who needs a cozy, uplifting story (like I did after certain early Nov events…) 📚💙

Monocytes and their doppelgängers: An immunological crossroads Monocyte research reveals “doppelgänger” populations that resemble classical monocytes but differ in origin, function, or migration.

Up next in highlights from this month's #ScienceImmunology was a Focus commentary from Alexander Mildner and Simon Yona discussing the challenges of mapping the identities of recently described #monocyte subsets with different origins and functions.

An exciting PhD opportunity in a great collaboration between @noelresearchlab.bsky.social and my lab looking at heart infections in zebrafish. Details below. Deadline is the 13th December. www.findaphd.com/phds/project...

My piece of advice for rotating students is to talk to older students who didn’t join the lab you’re considering. Most often they just found a better fit elsewhere - but it’s always a great sign when the students who didn’t join have positive things to say about their experience.

And here’s the rest! A list of ECRs in the #zebrafish community 😎 Reach out if you think you should be added 🙏 🧪 go.bsky.app/HwxuHey

tenure track assistant professor advertisement for Integrative Immunobiology department at Duke for tumor immunology

Duke Integrative Immunobiology department and Pharmacology & Cancer Biology joint search for tenure track assistant professor with focus on tumor immunology.

Katara!! 🌊

TB reclaims title of deadliest infectious disease. That's an 'outrage' says WHO DIslodged by COVID early in the pandemic, tuberculosis is once again the infectious disease that takes the most lives each year. And the number of cases set a new record. What's going on?

“Money reigns as perhaps the biggest obstacle” 🧪🩺

PhD dissertation title slide: Alterations in macrophage motility underlying disseminated mycobacterial infection

Time to leap to bsky, here is my biggest life update: defending my PhD in @tobinlab.bsky.social over the summer! I have loved working on mycobacterial infection and cell bio in zebrafish and am interested in diversifying my zfish disease model knowledge & experience 🐟🔬

Sending out a #zebrafish signal 🚨 If you work with our favorite fish or similar fish models, we want to follow you! Help us connect 🙏