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Front. Immunol. | doi: 10.3389/fimmu.2018.02175

Growth hormone (GH) deficient mice with GHRH gene ablation are severely deficient in vaccine and immune responses against Streptococcus pneumoniae

 Vincent Geenen1, 2*, Khalil Farhat2, Gwennaëlle Bodart2,  Chantal R. Charlet2, Christophe Desmet1, 2, Michel Moutschen1, 2, Yves Beguin1, 2, Frédéric Baron1, 2, Pierrette Melin-Remont1, 2, Pascale Quatresooz1, 2, Daniel Desmecht1, 2, Jean-Claude Sirard3,  Roberto Salvatori4 and  Henri Martens2
  • 1Department of Biomedical and Preclinical Sciences, Université de Liège, Belgium
  • 2Université de Liège, Belgium
  • 3Institut Pasteur de Lille, France
  • 4Johns Hopkins Medicine, United States

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.

Keywords: Somatotrope axis, GHRH, GH, Streptococcus pneumonia, Thymus-independent antigen, Spleen

Received: 29 Jun 2018; Accepted: 03 Sep 2018.

Edited by:

Lee M. Wetzler, School of Medicine, Boston University, United States

Reviewed by:

Juraj Ivanyi, King's College London, United Kingdom
Manel Juan, Hospital Clínic de Barcelona, Spain  

Copyright: © 2018 Geenen, Farhat, Bodart, Charlet, Desmet, Moutschen, Beguin, Baron, Melin-Remont, Quatresooz, Desmecht, Sirard, Salvatori and Martens. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Prof. Vincent Geenen, Université de Liège, Department of Biomedical and Preclinical Sciences, Liège, B-4000, Liege, Belgium,