Systems-level characterization of EGFR kinase inhibitors reveals heterogeneous effects on Mtb-macrophage interactions.

ABSTRACT: Mycobacterium tuberculosis (Mtb) causes deadly, antibiotic-recalcitrant disease. Host-directed therapy (HDT) is a proposed, antibiotic-complementary approach that enhances host antimicrobial function, thereby restricting intracellular Mtb. Drug repurposing screens suggest that inhibiting epidermal growth factor receptor (EGFR) may improve macrophage restriction of Mtb. However, the role of EGFR in restriction is not well understood. We show EGFR kinase inhibitors are not generally Mtb-restrictive in human monocyte-derived macrophages. Few EGFR inhibitors restrict intracellular Mtb and do so via heterogeneous mechanisms, including direct antibiotic effects and host-dependent, likely EGFR-independent mechanisms. During host-dependent therapy, intracellular Mtb induce defined, stress-r

SUBMITTER: Gunnarsson C 

PROVIDER: S-EPMC12633013 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature