NETosis associates with human TB lung tissue destruction and disease pathogenesis

ABSTRACT: NETosis is a neutrophil-specific cell death characterized by release of neutrophil extracellular traps. The role of NETosis in TB disease pathogenesis is poorly understood. We analyzed human lung TB granuloma proteomics, which revealed enrichment of neutrophil-associated proteins in necrotic regions of caseous and cavitary granulomas. Using immunohistochemistry (IHC), we validated the abundance of neutrophil-associated proteins, including MPO, CYBB and NCF1, as well as NETosis markers, neutrophil elastase (NE) and citrullinated H3, in the necrotizing caseum. In-vitro drug inhibition assays were used to investigate potential drivers of NETosis, with pharmaceutical inhibition of MPO, NE and CYBB resulting in reduction of Mycobacterium tuberculosis (Mtb)-induced NETosis. Using RT-qPCR, we fou

SUBMITTER: Kimone, L Fisher 

PROVIDER: S-SCDT-10_1038-S44321-026-00435-3 | biostudies-other |

REPOSITORIES: biostudies-other