Route-dependent immune-inflammatory and tissue remodeling responses to BCG injection in mice

Bacillus Calmette-Guérin (BCG) activates innate immune responses, but its tissue effects depend on the route of administration. We compared intra-airway (IA) and intravenous (IV) BCG administration in female C57BL/6N mice using a matched longitudinal design from immediately after administration through day 28. Outcomes included body and organ weights, gross pathology, histology, collagen and iron deposition, and pulmonary inflammatory-marker expression. IA-BCG reduced body-weight gain and produced marked pulmonary inflammation, collagen deposition, and increased staining for inflammatory and fibrosis-related markers. IV-BCG caused minimal pulmonary injury but produced hepatosplenomegaly, periportal hepatic collagen deposition, splenic hemorrhage, and splenic iron accumulation. These findings define distinct route-associated tissue phenotypes under matched experimental conditions. IA administration provides a model for pulmonary inflammation and remodeling, whereas IV administration provides a model for hepato-splenic responses. Bacterial burden, immune-cell composition, and causal signaling pathways were not assessed.