Growth Hormone (GH) Deficient Mice With GHRH Gene Ablation Are Severely Deficient in Vaccine and Immune Responses Against Streptococcus pneumoniae

Autor: Vincent Geenen, Jean-Claude Sirard, Roberto Salvatori, Henri Martens, Gwennaëlle Bodart, Yves Beguin, Daniel Desmecht, Christophe Desmet, Khalil Farhat, Pierrette Melin, Frédéric Baron, Chantal Charlet-Renard, Anne-Simone Parent, Michel Moutschen, Pascale Quatresooz
Přispěvatelé: Université de Liège, Service d'Hématologie, Mission Climat de la Caisse des Dépôts - Carbon Offsets, Agriculture and Forestry Unit, Groupe caisse des dépots, Centre Hospitalier Universitaire de Liège (CHU-Liège), Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 (CIIL), Centre National de la Recherche Scientifique (CNRS)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Université de Lille-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Johns Hopkins University School of Medicine [Baltimore], This study was supported by grants from Association of Specialization and Scientific Guidance (Lebanon), Fonds National de la Recherche Scientifique (F.R.S-FNRS, Belgium), Fonds Léon Fredericq (Belgium), Wallonia (Germaine Tillon program of Wallonia Caregiver 1318184), and Federation Wallonia-Brussels (ARC Somasthym) for financial support. VG is Research director, FB is Senior Research Associate, and CD is Research Associate at the F.R.S-FNRS., We thank L. Duwez, F. Olivier, G. Lambert, and Pr. P. Drion from the GIGA Animal Facility for animal management, and Dr. S. Ormanese and R. Stephan from the Cell Imaging and Flow Cytometry GIGA Technological Platform for their help for flow cytometry experiments design and analyses. We are indebted to Pr. F. Mascart and Pr. A. Vanderplasschen for very fruitful discussions. We also thank Pfizer for kindly providing Genotonorm (recombinant hGH). A part of this study has been selected as oral presentation at the 2018 Meeting of the Endocrine Society (Chicago)., Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS), Sirard, Jean-Claude
Jazyk: angličtina
Rok vydání: 2018
Předmět:
Zdroj: Frontiers in Immunology
Frontiers in Immunology, Frontiers, 2018, 9, pp.2175. ⟨10.3389/fimmu.2018.02175⟩
Frontiers in Immunology, 2018, 9, pp.2175. ⟨10.3389/fimmu.2018.02175⟩
Frontiers in Immunology, Vol 9 (2018)
ISSN: 1664-3224
Popis: International audience; The precise impact of the somatotrope axis upon the immune system is still highly debated. We have previously shown that mice with generalized ablation of growth hormone (GH) releasing hormone (GHRH) gene (Ghrh -/-) have normal thymus and T-cell development, but present a marked spleen atrophy and B-cell lymphopenia. Therefore, in this paper we have investigated vaccinal and anti-infectious responses of Ghrh -/- mice against S. pneumoniae, a pathogen carrying T-independent antigens. Ghrh -/- mice were unable to trigger production of specific IgM after vaccination with either native pneumococcal polysaccharides (PPS, PPV23) or protein-PPS conjugate (PCV13). GH supplementation of Ghrh -/- mice restored IgM response to PPV23 vaccine but not to PCV13 suggesting that GH could exert a specific impact on the spleen marginal zone that is strongly implicated in T-independent response against pneumococcal polysaccharides. As expected, after administration of low dose of S. pneumoniae, wild type (WT) completely cleared bacteria after 24 h. In marked contrast, Ghrh -/- mice exhibited a dramatic susceptibility to S. pneumoniae infection with a time-dependent increase in lung bacterial load and a lethal bacteraemia already after 24 h. Lungs of infected Ghrh -/- mice were massively infiltrated by inflammatory macrophages and neutrophils, while lung B cells were markedly decreased. The inflammatory transcripts signature was significantly elevated in Ghrh -/- mice. In this animal model, the somatotrope GHRH/GH/IGF1 axis plays a vital and unsuspected role in vaccine and immunological defense against S. pneumoniae.
Databáze: OpenAIRE
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