Lmst

#cathepsin

#Tuberculosis severity varies widely between people; why is this? This study uses the #CollaborativeCross mouse panel to identify the protease #cathepsin Z (CTSZ) as a conserved regulator of #TB outcomes via its influence on CXCL1 in mice & in humans @PLOSBiology https://plos.io/4phwRA8

Human CTSZ variants are associated with TB severity, and CTSZ is present at the host-pathogen interface within human pulmonary Mtb granulomas. Top left: A manually annotated UMAP generated by unsupervised clustering of data from single-cell mRNA-Seq of human biopsy tissue, containing Mtb granulomas from three patients with TB. Top right: Analysis of normalized expression values reveals that CTSZ is specifically induced in granuloma macrophages, particularly in lipid-associated macrophages. Bottom: Brightfield (BF) images and immunofluorescent staining of CTSZ and CD68 within a granuloma biopsy from an individual with pulmonary TB. Goat (Gt) and mouse (Ms) IgG isotype control staining is depicted in the top row. DAPI staining indicates cell nuclei. Scale bar is 60 µM in length.

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