Salmonella synthesizing 1-monophosphorylated lipopolysaccharide infection challenge induces immunomodulatory innate immune responses in murine antigen presenting cells 4229

Abstract Description Salmonella is a zoonic pathogen of critical public health concern and increasing antibiotic resistance, prompting the need for alternative preventative approaches against infection. Host-derived small extracellular vesicles (sEVs) coordinate cell-to-cell communication, prime immune responses, and transfer immunomodulatory cargo during Salmonella infection. Salmonella Typhimurium synthesizing 1-dephosphorylated lipid A (S.TmMPL) elicits reduced endotoxic activity while retaining immunogenicity. We hypothesize S.TmMPL infection induces differential responses in antigen presenting cells compared to wild-type Salmonella (S.TmWT). Mice were orally challenged with S.TmWT, S.TmMPL, or mock-infected. At 3 days post-challenge, bacterial burdens in organs were quantified and dendritic cell (DC) subsets were characterized in small intestines (SIs) across conditions. sEVs from S.TmWT or S.TmMPL-infected RAW264.7 macrophages (MΦ) were isolated 24-hours post infected and subjected to nanoparticle tracking and protein analysis. Bacterial burden of the spleen, lungs, and SIs tissues of S.TmMPL-infected mice show reduced titers compared to S.TmWT. S.TmMPL-infected SIs are enriched in CD103+ DCs and reduced for inflammatory-DC subsets. S.TmMPL-infected MΦs elicited reduced sEV production along expression of endosomal compartment-associated markers. In summary, S.TmMPL infection leads to reduced local and septic bacterial morbidity, shift in local DC subsets, and modulation of sEV induction. Funding Sources Supported by NIH/NIAID AI-158749 Topic Categories Mucosal and Regional Immunology (MUC)