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Severe deficiency of the somatotrope GHRH/GH/IGF-1 axis induces a dramatic susceptibility to Streptococcus pneumoniae infection.
Farhat, Khalil; Bodart, Gwennaëlle; Desmet, Christophe et al.
2016Growth Hormone Research Society (GRS) and IGF Society
 

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Keywords :
Growth Hormone Releasing Hormone; Growth Hormone; IGF-1; Streptococcus pneumoniae
Abstract :
[en] Deletion of the growth hormone-releasing hormone gene (Ghrh) results in a severe deficiency of the somatotrope GHRH-GH-IGF-1 axis causing dwarf phenotype that can be reversed by GH or GHRH supplementation (Alba & Salvatori, Endocrinology 2004;145:4134). In basal conditions, the immunological phenotype of Ghrh-/- mice is not markedly disturbed except for a decrease in B cells and an increase in generation of thymic (t) Treg cells (submitted for publication). These data prompted us to investigate immune responses of Ghrh-/- mice using vaccination and infection by S. pneumoniae as models since the response to both stimuli rely on the innate immune system and B cells. Ghrh-/- mice were unable to trigger production of specific IgM and IgG against serotype 1 pneumococcal polysaccharide (PPS) after vaccination with either native PPS (Pnx23) or protein-PPS conjugate (Prev-13) vaccines. A short GH supplementation to Ghrh-/- mice (1 daily injection of 1 mg/kg GH for 4 weeks) restored IgM and IgG response to Pnx23 vaccine but not to Prev-13. This suggests that GH differently impacts on B-1, marginal zone B-2 or innate B-1 B cells. Furthermore, after intranasal instillation of a non-lethal dose of serotype 1 S. pneumoniae, Ghrh-/- mice exhibited a dramatic susceptibility reflected by bacteremia 24h after infection and a survival limit of 72 h, compared to WT C57BL/6 mice that need only 24h to clear infection. The possible impact of GH deficiency on components of the innate immune system that play an important role in defense of the respiratory tract against pneumococcal infection is under current investigation. (*Equal first and last authors. KF is supported by a research grant from the Lebanese Government; GB is Research Assistant, CD is Research Associate, and VG is Research Director at the NFSR of Belgium).
Research center :
GIGA-I3 - Giga-Infection, Immunity and Inflammation - ULiège
Disciplines :
Immunology & infectious disease
Endocrinology, metabolism & nutrition
Author, co-author :
Farhat, Khalil ;  Université de Liège - ULiège > Form. doc. sc. bioméd. & pharma.
Bodart, Gwennaëlle ;  Université de Liège > Centre d'immunologie
Desmet, Christophe  ;  Université de Liège > Département des sciences fonctionnelles (DSF) > GIGA-R : Biochimie et biologie moléculaire
Moutschen, Michel  ;  Université de Liège > Département des sciences cliniques > GIGA-R:Immunopath. - Maladies infect. et médec. inter. gén.
Salvatori, Roberto;  Johns Hopkins University > Endocrinology
Geenen, Vincent ;  Université de Liège > Centre d'immunologie
Martens, Henri ;  Université de Liège > Centre d'immunologie
Language :
English
Title :
Severe deficiency of the somatotrope GHRH/GH/IGF-1 axis induces a dramatic susceptibility to Streptococcus pneumoniae infection.
Publication date :
07 November 2016
Event name :
Growth Hormone Research Society (GRS) and IGF Society
Event organizer :
GRS
Event place :
Tel Aviv, Israel
Event date :
6 au 9 novembre 2016
Audience :
International
Additional URL :
Name of the research project :
SOMASTHYM - The somatotrope GHRH/GH/IGF1 axis and immune reconstitution through thymus recovery.
Funders :
F.R.S.-FNRS - Fonds de la Recherche Scientifique [BE]
ARC - Somasthym
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since 03 November 2016

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