Tissue-wide profiling of human lungs reveals spatial sequestration of macrophages in tuberculosis The immune response to human tuberculosis (TB), particularly in the context of complex lung pathology, remains incompletely understood. Here, we employed whole-slide spatial proteomics to map immune c...

New preprint from my lab on mapping immune cell organization in the lungs of tuberculosis patients using spatial proteomics, a productive collaboration with Xinchun Chen lab and @ellispatrick.bsky.social
www.biorxiv.org/content/10.1...

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...

We've known about the gut-brain axis.
Now we're learning about the gut-brain-lung axis whereby food intake can trigger an immune response in the airway. www.cell.com/neuron/fullt...

B cells in non-lymphoid tissues - Nature Reviews Immunology B cells are major drivers of systemic immunity, but they also act locally in non-lymphoid organs. This Review highlights new insights into mechanisms of tissue B cell function as well as efforts to le...

Review @natrevimmunol.bsky.social @laurenrodda.bsky.social @georgecelis.bsky.social
B cells in non-lymphoid tissues
www.nature.com/articles/s41...

Interested in Mtb pathogenesis and developing new strategies to treat these deadly infections? Please apply to join us for the GRC for Tuberculosis Drug Discovery and Development!! www.grc.org/tuberculosis...
Deadline to submit an abstract to be considered for a talk is March 1st! Please repost!

1/ We are excited to share our new paper in @jexpmed.bsky.social about humans with autosomal dominant IFNAR1 deficiency (doi.org/10.1084/jem....).

Cold Spring Harbor Asia meeting on Mycobacterial Pathogenesis and Host Response, Suzhou, China, March 17-21, 2025. Abstract deadline Jan 10, 2025. www.csh-asia.org?content/2606

Immunopathology in human tuberculosis The balance between protective and pathological immune responses shapes progression of Mycobacterium tuberculosis infection.

Interested in the immunopathology of human tuberculosis? Here is our latest review:
www.science.org/doi/10.1126/...

Could you please add me to the pack, thanks

Please add me to the party

Applications are open for the 2025 TB drug discovery & development GRC!! We have an awesome line-up of speakers and multiple open talk slots that will be filled based on abstract submissions. Apply now to join us for this fantastic conference!! www.grc.org/tuberculosis...

Spatially restricted immune and microbiota-driven adaptation of the gut - Nature Intestinal regionalization is characterized by robust and resilient structural cell states and the intestine can adapt to environmental stress in a spatially controlled manner through crosstalk betwee...

#WeekendRead! #LocationLocationLocation! Amazing @Nature by @touficmayassi.bsky.social, Xavier &co showing regional specialization of the gut at the spatial (single cell) level! Strong resilience after inflammation & ILC2 are key in middle colon adaption to microbiota! www.nature.com/articles/s41...

LTβR deficiency causes lymph node aplasia and impaired B cell differentiation Loss-of-function mutations in LTBR result in a stromal defect, leading to dysfunctional secondary lymphoid organs and combined immunodeficiency in humans.

www.science.org/doi/10.1126/...

Could you please add me to the list, thanks.