Dysregulation of Stress Erythropoiesis and Enhanced Susceptibility to Salmonella Typhimurium Infection in Aryl Hydrocarbon Receptor–Deficient Mice.

This article investigates the role of the aryl hydrocarbon receptor (AhR), a ligand-induced transcription factor involved in immune regulation, in chronic systemic infection with an attenuated strain of Salmonella Typhimurium (STM) called TAS2010. Using AhR-deficient (AhR−/−) and wild type (WT) mice, the study found that AhR−/− mice exhibited increased susceptibility to TAS2010 infection, characterized by higher bacterial loads, increased mortality, and impaired bacterial clearance. AhR−/− mice developed macrocytic anemia and pronounced splenomegaly due to enhanced stress erythropoiesis in the spleen, driven by elevated serum levels of erythropoietin (EPO) and interleukin 6 (IL-6), alongside disrupted splenic architecture. These findings suggest that AhR deficiency compromises host defense against chronic STM infection by promoting excessive stress erythropoiesis and splenic remodeling, which may impair effective immune responses.