Granuloma Dual RNA-Seq Reveals Composite Transcriptional Programs Driven by Neutrophils and Necrosis within Tuberculous Granulomas.

ABSTRACT: Mycobacterial granulomas lie at the center of tuberculosis (TB) pathogenesis and represent a unique niche where infecting bacteria survive in nutrient-restricted conditions and in the face of a host immune response. The granuloma's necrotic core, where bacteria reside extracellularly in humans, is difficult to assess in many experimentally tractable models. Here, using necrotic mycobacterial granulomas in adult zebrafish, we develop dual RNA-seq across different host genotypes to identify the transcriptional alterations that enable bacteria to survive within this key microenvironment. Through pharmacological and genetic interventions, we find that neutrophils within mature, necrotic granulomas promote bacterial growth, in part through upregulation of the bacterial devR regulon. We i

SUBMITTER: Viswanathan G 

PROVIDER: S-EPMC12087985 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature