Host TGF-β signalling facilitates Vi-capsule mediated adaptive immune evasion and vertical transmission of Salmonella Typhi in Caenorhabditis elegans.

Bacterial infections trigger robust host immune responses, while pathogens concurrently adapt to enhance survival within the host. In our previous study, we observed 24 h of Salmonella Typhi infection in Caenorhabditis elegans colonized the body of the host and also vertically transmitted to their F1 offspring generation. This study investigates host interaction-mediated modulation in S. Typhi physiology and virulence, focusing on host-derived strains from initial infection (CeP0-ST) and vertically transmitted F1 progeny (CeF1-ST), compared to the wild-type unexposed strain (WT-ST). We employed C. elegans lifespan assays, bacterial colonization, morphology, motility, gene expression, ROS estimation, and infection models using immune pathway mutants. CeP0-ST and CeF1-ST exhibited increased infectivity, faster mortality, and enhanced colonization, accompanied by reduced cell size, motility, and lipopolysaccharide (LPS)-mediated immunogenicity. This was evidenced by downregulation of fliC, ompC, ompF, and SPI-1 encoded Type III Secretion System (T3SS-1) genes (sipA, avrA, sopE). Upregulation of Vi-capsular antigen genes (tviD, tviA, viaB) suggested immune evasion, which was supported by improved host survival upon Vi-negative Ty21a strain infection. Among various C. elegans immune pathway mutants, the TGF-β pathway mutant [sma-6(-)] showed altered pathogen modulation, with reduced Vi expression and increased T3SS gene expression in derived strains. Suppressed host immune gene expression during WT-derived infections, but increased expression during sma-6 (-)-derived infections, suggests a role for TGF-β signalling in driving pathogen adaptation. These findings highlight that host interaction promotes S. Typhi immune evasion via Vi-antigen expression, potentially regulated by host TGF-β signalling, and that vertical transmission of adapted strains facilitates long-term persistence.