Serum from Laron Mice Partially Protects against Trypanosoma Cruzi Infection

Chagas disease (CD) is one of the most devasting parasitic diseases in the Americas affecting 7 to 8 million people worldwide. In vitro and in vivo experiments have demonstrated that decreased growth hormone (GH) serum levels occur as CD progresses. Interestingly, inactivating mutations in the GH receptor in humans induce Laron syndrome (LS), a clinical entity characterized by increased GH and decreased insulin growth factor-1 (IGF-1) serum levels. The largest cohort of LS subjects lives in the southern provinces of Ecuador. Remarkably, CD prevalence in these individuals is diminished 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 T. cruzi infection. We infected mouse fibroblast L-cells treated with serum from each type of mouse with metacyclic trypomastigotes from Trypanosoma cruzi (etiological CD infectious agent). Treatment with GHR-/- serum (LS mice) significantly decreased infection by 28% compared to 48% seen in control wild-type mouse serum (WT). Treatment with bGH mouse serum significantly decreased infection by only 41% compared to 54% from WT controls. Our results suggest that high GH and low IGF-1 in blood circulation, as typically seen in LS individuals, confers partial protection against T. cruzi infection.