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Front. Cell. Infect. Microbiol. | doi: 10.3389/fcimb.2019.00311

Macrophages from subjects with isolated GH/IGF-I deficiency due to a GHRH receptor gene mutation are less prone to infection by Leishmania amazonensis.

  • 1Division of Immunology and Molecular Biology Laboratory, Federal University of Sergipe, Brazil
  • 2Federal University of Sergipe, Brazil
  • 3Department of Microbiology, Institute of Biological Sciences, Federal University of Minas Gerais, Brazil
  • 4Laboratory of Seroepidemiology and Immunobiology, Institute of Tropical Medicine of São Paulo, University of São Paulo, Brazil
  • 5Division of Endocrinology, Diabetes, & Metabolism, School of Medicine, Johns Hopkins University, United States

Isolated growth hormone (GH) deficiency (IGHD) affects approximately 1 in 4,000 to 1 in 10,000 individuals worldwide. We have previously described a large cohort of subjects with IGHD due to a homozygous mutation in the GH releasing hormone (GHRH) receptor gene. These subjects exhibit throughout the life very low levels of GH and its principal mediator, the Insulin Growth Factor-I (IGF-I). The facilitating role of IGF-I in the infection of mice macrophages by different Leishmania strains is well known. Nevertheless, the role of IGF-I in Leishmania infection of human macrophages has not been studied. This study aimed to evaluate the behavior of Leishmania infection in vitro in macrophages from untreated IGHD subjects. To this end, blood samples were collected from 14 IGHD individuals and 14 age and sex-matched healthy controls. Monocytes were isolated and derived into macrophages and infected with a strain of Leishmania amazonensis. In addition, IGF-I was added to culture medium to evaluate its effect on the infection. Cytokines were measured in the culture supernatants. We found that macrophages from IGHD subjects were more resistant to Leishmania infection compared to GH sufficient controls. Both inflammatory and anti-inflammatory cytokines increase only in the supernatants of the control macrophages. Addition of IGF-I to the culture medium increased infection rates. In conclusion, we demonstrated that IGF-I is crucial for Leishmania infection of human macrophages.

Keywords: growth hormone deficiency, Insulin Growth Factor-I deficiency, Macrophages, Leishmaniasis, Phagocytosis, Infection, immunology

Received: 20 Apr 2019; Accepted: 16 Aug 2019.

Copyright: © 2019 Barrios, Campos, Peres, Oliveira, Cazzaniga, Santos, Aires, Silva, Barreto, Goto, De Almeida, Salvatori, Aguiar-Oliveira and De Jesus. 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. Amélia R. De Jesus, Division of Immunology and Molecular Biology Laboratory, Federal University of Sergipe, Aracaju, Brazil,