title: Escherichia coli Nissle 1917 protects gnotobiotic pigs against human rotavirus by modulating pDC and NK-cell responses.
abstract: Lactobacillus rhamnosus GG (LGG), a gram-positive lactic acid bacterium, is one of the most widely used probiotics; while fewer gram-negative probiotics including Escherichia coli Nissle 1917 (EcN) are characterized. A mechanistic understanding of their individual and interactive effects on human rotavirus (HRV) and immunity is lacking. In this study, noncolonized, EcN-, LGG-, and EcN + LGG-colonized neonatal gnotobiotic (Gn) pigs were challenged with HRV. EcN colonization is associated with a greater protection against HRV, and induces the highest frequencies of plasmacytoid dendritic cells (pDCs), significantly increased NK-cell function and decreased frequencies of apoptotic and TLR4+mononuclear cells (MNCs). Consistent with the highest NK-cell activity, splenic CD172+MNCs (DC enriched fraction) of EcN-colonized pigs produced the highest levels of IL-12 in vitro. LGG colonization has little effect on the above parameters, which are intermediate in EcN + LGG-colonized pigs, suggesting that probiotics modulate each other's effects. Additionally, in vitro EcN-treated splenic or intestinal MNCs produce higher levels of innate, immunoregulatory and immunostimulatory cytokines, IFN-α, IL-12, and IL-10, compared to MNCs of pigs treated with LGG. These results indicate that the EcN-mediated greater protection against HRV is associated with potent stimulation of the innate immune system and activation of the DC-IL-12-NK immune axis.
authors.affiliation: Veterinary Preventive Medicine Department, Food Animal Health Research Program (FAHRP), The Ohio Agricultural Research and Development Center, The Ohio State University, Wooster, OH, USA. vlasova.1@osu.edu.
authors.forename: Anastasia N
authors.initials: AN
authors.lastname: Vlasova
authors.affiliation: Veterinary Preventive Medicine Department, Food Animal Health Research Program (FAHRP), The Ohio Agricultural Research and Development Center, The Ohio State University, Wooster, OH, USA.
authors.forename: Lulu
authors.initials: L
authors.lastname: Shao
authors.affiliation: Veterinary Preventive Medicine Department, Food Animal Health Research Program (FAHRP), The Ohio Agricultural Research and Development Center, The Ohio State University, Wooster, OH, USA.
authors.forename: Sukumar
authors.initials: S
authors.lastname: Kandasamy
authors.affiliation: Veterinary Preventive Medicine Department, Food Animal Health Research Program (FAHRP), The Ohio Agricultural Research and Development Center, The Ohio State University, Wooster, OH, USA.
authors.forename: David D
authors.initials: DD
authors.lastname: Fischer
authors.affiliation: Veterinary Preventive Medicine Department, Food Animal Health Research Program (FAHRP), The Ohio Agricultural Research and Development Center, The Ohio State University, Wooster, OH, USA.
authors.forename: Abdul
authors.initials: A
authors.lastname: Rauf
authors.affiliation: Veterinary Preventive Medicine Department, Food Animal Health Research Program (FAHRP), The Ohio Agricultural Research and Development Center, The Ohio State University, Wooster, OH, USA.
authors.forename: Stephanie N
authors.initials: SN
authors.lastname: Langel
authors.affiliation: Veterinary Preventive Medicine Department, Food Animal Health Research Program (FAHRP), The Ohio Agricultural Research and Development Center, The Ohio State University, Wooster, OH, USA.
authors.forename: Kuldeep S
authors.initials: KS
authors.lastname: Chattha
authors.affiliation: Veterinary Preventive Medicine Department, Food Animal Health Research Program (FAHRP), The Ohio Agricultural Research and Development Center, The Ohio State University, Wooster, OH, USA.
authors.forename: Anand
authors.initials: A
authors.lastname: Kumar
authors.affiliation: Veterinary Preventive Medicine Department, Food Animal Health Research Program (FAHRP), The Ohio Agricultural Research and Development Center, The Ohio State University, Wooster, OH, USA.
authors.forename: Huang-Chi
authors.initials: HC
authors.lastname: Huang
authors.affiliation: Veterinary Preventive Medicine Department, Food Animal Health Research Program (FAHRP), The Ohio Agricultural Research and Development Center, The Ohio State University, Wooster, OH, USA.
authors.forename: Gireesh
authors.initials: G
authors.lastname: Rajashekara
authors.affiliation: Veterinary Preventive Medicine Department, Food Animal Health Research Program (FAHRP), The Ohio Agricultural Research and Development Center, The Ohio State University, Wooster, OH, USA.
authors.forename: Linda J
authors.initials: LJ
authors.lastname: Saif
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D003602:Cytotoxicity, Immunologic; D003713:Dendritic Cells / Q000276:immunology* / Q000821:virology; D004926:Escherichia coli / Q000276:immunology*; D004927:Escherichia coli Infections / Q000276:immunology*; D005856:Germ-Free Life; D006801:Humans; D007113:Immunity, Innate; D018836:Inflammation Mediators / Q000378:metabolism; D007413:Intestinal Mucosa / Q000276:immunology*; D007694:Killer Cells, Natural / Q000276:immunology*; D052201:Lacticaseibacillus rhamnosus / Q000276:immunology*; D008213:Lymphocyte Activation; D019936:Probiotics; D012401:Rotavirus / Q000276:immunology*; D012400:Rotavirus Infections / Q000276:immunology*; D013552:Swine
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators
keywords: Childhood diarrhea; Dendritic cells; E. coli Nissle 1917; Human rotavirus; L. rhamnosus GG; Natural killer cells; Probiotics