Escherichia coli Nissle 1917 colonization upregulates innate immunity and partially protects against human rotavirus infection in a neonatal gnotobiotic pig model (INC7P.422)

Abstract We evaluated how colonization with gram-positive or gram-negative commensal bacteria (alone or combined) modulates virulent human rotavirus (VirHRV) infection and innate immunity in a neonatal gnotobiotic (Gn) pig model. Gn pigs were colonized with Escherichia coli Nissle 1917 (EcN), Lactobacillus rhamnosus GG (LGG) or both (EcN+LGG) and challenged with VirHRV 15 days later. Non-colonized VirHRV challenged pigs served as controls. Colonization with each bacteria alone or combined, decreased VirHRV shedding and diarrhea scores post-challenge. Among the colonized pigs, those were lowest in the EcN-, intermediate in EcN+LGG- and highest in the LGG-colonized pigs. EcN colonization induced the highest plasmacytoid dendritic cell (DC) frequencies (EcN or EcN+LGG, all tissues), significantly increased natural killer (NK) cell activity (EcN, spleen and blood) and decreased frequencies of VirHRV-induced apoptotic and TLR4+ mononuclear cells (MNCs) (EcN, all tissues). Consistent with the highest NK cell activity, SWC3a+ MNCs (DC enriched fraction) from spleen of EcN colonized Gn pigs produced the highest levels of IL12 (essential for NK cell activation) in vitro. LGG colonization had less effect on VirHRV induced innate immune responses, and those of EcN+LGG colonized pigs were intermediate, suggesting that LGG and EcN modulate each other’s effects. Our results indicate that EcN partially protects against VirHRV infection and diarrhea by modulating innate immune responses.