title: Immunostimulatory effects of recombinant Erysipelothrix rhusiopathiae expressing porcine interleukin-18 in mice and pigs.
abstract: Interleukin-18 (IL-18), which was originally called gamma interferon (IFN-γ)-inducing factor, has been shown to play an important role in innate and acquired immune responses. In this study, attenuated Erysipelothrix rhusiopathiae strains were engineered to produce porcine IL-18 (poIL-18) and evaluated for their potential immunostimulatory effect in animals. Recombinant poIL-18 was successfully expressed in the recombinant E. rhusiopathiae strains YS-1/IL-18 and KO/IL-18. The culture supernatant of YS-1/IL-18 was confirmed to induce IFN-γ production in murine splenocytes in vitro, and this production was inhibited by incubation with anti-poIL-18 monoclonal antibodies. Furthermore, more IFN-γ production was induced upon stimulation of splenocytes with concanavalin A for splenocytes from mice that were intraperitoneally inoculated with YS-1/IL-18 than for splenocytes from control mice inoculated with the parent strain YS-1. Peritoneal macrophages from mice preinoculated with YS-1/IL-18 exhibited enhanced phagocytosis of Salmonella enterica subsp. enterica serovar Typhimurium compared with peritoneal macrophages from control mice preinoculated with YS-1. We also confirmed the immunostimulatory effect on humoral immune responses against antigens of E. rhusiopathiae and Mycoplasma hyopneumoniae in gnotobiotic pigs that were orally preinoculated with KO/IL-18. Thus, these results provide evidence that E. rhusiopathiae is a promising vector for the expression of host cytokines and suggest the potential utility of E. rhusiopathiae vector-encoded cytokines in the activation of host innate and acquired immune responses.
authors: National Institute of Animal Health, National Agriculture and Food Research Organization, Tsukuba, Ibaraki, Japan.
authors: Yohsuke
authors: Y
authors: Ogawa
authors: Yu
authors: Y
authors: Minagawa
authors: Fang
authors: F
authors: Shi
authors: Masahiro
authors: M
authors: Eguchi
authors: Yoshihiro
authors: Y
authors: Muneta
authors: Yoshihiro
authors: Y
authors: Shimoji
mesh_terms: D000818:Animals; D001428:Bacterial Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D004888:Erysipelothrix / Q000235:genetics / Q000276:immunology*; D005260:Female; D020382:Interleukin-18 / Q000235:genetics / Q000276:immunology*; D007963:Leukocytes, Mononuclear / Q000276:immunology; D017737:Macrophages, Peritoneal / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D010587:Phagocytosis; D013154:Spleen / Q000276:immunology; D013552:Swine; D014613:Vaccines, Attenuated / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology
chemical_list: D001428:Bacterial Vaccines; D020382:Interleukin-18; D014613:Vaccines, Attenuated; D014614:Vaccines, Synthetic