title: Synthetic human chorionic gonadotropin-related oligopeptides impair early innate immune responses to Listeria monocytogenes in Mice.
abstract: Background. Synthetic human chorionic gonadotropin (hCG)-related oligopeptides are potent inhibitors of pathogenic inflammatory responses induced by in vivo lipopolysaccharide exposure or hemorrhagic shock-induced injury. In this study, we tested whether hCG-related oligopeptide treatment similarly altered inflammatory responses and innate host defenses in mice during experimental Listeria monocytogenes infection. Methods. Mice were infected with L. monocytogenes and treated with hCG-related oligopeptides (LQGV, VLPALP, or AQGV) or phosphate-buffered saline. Subsequently, mice were analyzed for bacterial loads, cytokine and chemokine responses, and inflammatory cell infiltrates in target organs. Results. Oligopeptide administration increased bacterial numbers in the spleen and liver at 6 h after infection. Simultaneously, CXCL1/KC and CCL2/MCP-1 plasma levels as well as neutrophil numbers in the spleen, blood, and peritoneal cavity decreased. In contrast, at 18 h after infection, systemic tumor necrosis factor alpha, interleukin 12 p70, interleukin 6, and interferon gamma levels increased statistically significantly in oligopeptide-treated mice compared with controls, which correlated with increased bacterial numbers. Conclusion. These data show that treatment with hCG-related oligopeptides (LQGV, VLPALP, and AQGV) inhibits early innate immune activation by reducing initial chemokine secretion following infection. This leads to bacterial overgrowth with subsequent enhanced systemic inflammation. Our data underscore the importance of early innate immune activation and suggest a role for hCG-derived oligopeptides at the placenta that increases the risk of L. monocytogenes infections.
authors.affiliation: Department of Immunology, Erasmus Medical Center, 3000 CA Rotterdam, the Netherlands.
authors.forename: Marten
authors.initials: M
authors.lastname: van der Zee
authors.forename: Willem A
authors.initials: WA
authors.lastname: Dik
authors.forename: Yolanda S
authors.initials: YS
authors.lastname: Kap
authors.forename: Marilyn J
authors.initials: MJ
authors.lastname: Dillon
authors.forename: Robbert
authors.initials: R
authors.lastname: Benner
authors.forename: Pieter J M
authors.initials: PJ
authors.lastname: Leenen
authors.forename: Nisar A
authors.initials: NA
authors.lastname: Khan
authors.forename: Douglas A
authors.initials: DA
authors.lastname: Drevets
mesh_terms: D000818:Animals; D018925:Chemokines / Q000097:blood / Q000276:immunology; D006063:Chorionic Gonadotropin / Q000494:pharmacology*; D015169:Colony Count, Microbial; D016207:Cytokines / Q000097:blood / Q000276:immunology; D004195:Disease Models, Animal; D006801:Humans; D007113:Immunity, Innate / Q000187:drug effects; D008089:Listeria monocytogenes / Q000276:immunology*; D008088:Listeriosis / Q000188:drug therapy* / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009154:Mutation; D020556:Neutrophil Infiltration / Q000187:drug effects; D009842:Oligopeptides / Q000494:pharmacology*; D011994:Recombinant Proteins / Q000494:pharmacology
chemical_list: D018925:Chemokines; D006063:Chorionic Gonadotropin; D016207:Cytokines; D009842:Oligopeptides; D011994:Recombinant Proteins