High growth hormone serum partially protects mice against Trypanosoma cruzi infection

Chagas disease (CD) is one of the most devasting parasitic diseases in the Americas, affecting 7–8 million people worldwide. In vitro and in vivo experiments have demonstrated that growth hormone (GH) serum levels decrease as CD progresses. Interestingly, inactivating mutations in the GH receptor in...

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Veröffentlicht in:FEBS open bio 2023-07, Vol.13 (7), p.1346-1356
Hauptverfasser: Mora‐Criollo, Patricia, Basu, Reetobrata, Qian, Yanrong, Funk, Kevin, Bell, Stephen, Young, Jonathan A., List, Edward O., Costales, Jaime A., Guevara‐Aguirre, Jaime, Grijalva, Mario J., Kopchick, John J.
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Sprache:eng
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Zusammenfassung:Chagas disease (CD) is one of the most devasting parasitic diseases in the Americas, affecting 7–8 million people worldwide. In vitro and in vivo experiments have demonstrated that growth hormone (GH) serum levels decrease as CD progresses. Interestingly, inactivating mutations in the GH receptor in humans result in Laron syndrome (LS), a clinical entity characterized by increased serum levels of GH and decreased insulin growth factor‐1 (IGF‐1). The largest cohort of LS subjects lives in the southern provinces of Ecuador. Remarkably, no clinical CD cases have been reported in these individuals despite living in highly endemic areas. In the current ex vivo study, we employed serum from GHR−/− mice, also known as LS mice (a model of GH resistance with high GH and low IGF‐1 levels), and serum from bovine GH (bGH) transgenic mice (high GH and IGF‐1), to test the effect on Trypanosoma cruzi infection. We infected mouse fibroblast L‐cells with T. cruzi (etiological CD infectious agent) and treated them with serum from each mouse type. Treatment with GHR−/− serum (LS mice) significantly decreased L‐cell infection by 28% compared with 48% from control wild‐type mouse serum (WT). Treatment with bGH mouse serum significantly decreased infection of cells by 41% compared with 54% from WT controls. Our results suggest that high GH and low IGF‐1 in blood circulation, as typically seen in LS individuals, confer partial protection against T. cruzi infection. This study is the first to report decreased T. cruzi infection using serum collected from two modified mouse lines with altered GH action (GHR−/− and bGH). High growth hormone (GH) serum collected from GHR−/− mice, also called Laron mice (LS) [high GH and low insulin growth factor‐1 (IGF‐1) levels] and transgenic bovine GH mice (high GH and low IGF‐1 levels), significantly decreased Trypanosoma cruzi infection in fibroblast L‐cells. Altered GH action (high GH) seems to play a protective role during T. cruzi infection, the parasite responsible for Chagas disease.
ISSN:2211-5463
2211-5463
DOI:10.1002/2211-5463.13627