[en] 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.
Research Center/Unit :
GIGA-I3 - Giga-Infection, Immunity and Inflammation - ULiège
Melin, Pierrette ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Bactériologie, mycologie, parasitologie, virologie
Quatresooz, Pascale ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Histologie
Parent, Anne-Simone ; Université de Liège - ULiège > Département des sciences cliniques > Pédiatrie
Desmecht, Daniel ; Université de Liège - ULiège > Département de morphologie et pathologie (DMP) > Pathologie spéciale et autopsies
Sirard, Jean-Claude; Institut Pasteur Lille
Salvatori, Roberto; Johns Hopkins
Martens, Henri ; Université de Liège - ULiège > Centre d'immunologie
Geenen, Vincent ; Université de Liège - ULiège > Centre d'immunologie
F.R.S.-FNRS - Fonds de la Recherche Scientifique [BE] Fonds Léon Fredericq [BE] DGTRE - Région wallonne. Direction générale des Technologies, de la Recherche et de l'Énergie [BE] Fédération Wallonie-Bruxelles (ARC Somasthym) Association of Specialization and Scientific Guidance (Lebanon)
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