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: Marten van der Zee, Willem A Dik, Yolanda S Kap, Marilyn J Dillon, Robbert Benner, Pieter J M Leenen, Nisar A Khan, Douglas A Drevets
• Journal: The Journal of infectious diseases (J Infect Dis) Vol. 201 Issue 7 Pg. 1072-80 (Apr 01 2010) ISSN: 1537-6613 [Electronic] United States
• PMID: 20170375 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Chemokines
• Chorionic Gonadotropin
• Cytokines
• Oligopeptides
• Recombinant Proteins

Topics

• Animals
• Chemokines (blood, immunology)
• Chorionic Gonadotropin (pharmacology)
• Colony Count, Microbial
• Cytokines (blood, immunology)
• Disease Models, Animal
• Humans
• Immunity, Innate (drug effects)
• Listeria monocytogenes (immunology)
• Listeriosis (drug therapy, immunology)
• Mice
• Mice, Inbred C57BL
• Mutation
• Neutrophil Infiltration (drug effects)
• Oligopeptides (pharmacology)
• Recombinant Proteins (pharmacology)