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

Mônica R. Barrios, Viviane C. Campos, Nalu T.A. Peres, Laís L. de Oliveira, Rodrigo A. Cazzaniga, Márcio B. Santos, Murilo B. Aires, Ricardo L.L. Silva, Aline Barreto, Hiro Goto, Roque P. Almeida, Roberto Salvatori, Manuel H. Aguiar-Oliveira, Amélia M.R. Jesus

Research output: Contribution to journalArticle

Abstract

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 mouse 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 less prone 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.

Original languageEnglish (US)
Article number311
JournalFrontiers in Cellular and Infection Microbiology
Volume9
Issue numberAUG
DOIs
StatePublished - Jan 1 2019

Fingerprint

Leishmania
Growth Hormone
Intercellular Signaling Peptides and Proteins
Macrophages
Insulin
Mutation
Infection
Genes
Culture Media
Pituitary Dwarfism
Cytokines
Monocytes
Anti-Inflammatory Agents

Keywords

  • Growth hormone deficiency
  • Immunology
  • Infection
  • Insulin growth factor-I deficiency
  • Leishmaniasis
  • Macrophages
  • Phagocytosis

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Microbiology (medical)
  • Infectious Diseases

Cite this

Macrophages from subjects with isolated GH/IGF-I deficiency due to a ghrh receptor gene mutation are less prone to infection by Leishmania amazonensis. / Barrios, Mônica R.; Campos, Viviane C.; Peres, Nalu T.A.; de Oliveira, Laís L.; Cazzaniga, Rodrigo A.; Santos, Márcio B.; Aires, Murilo B.; Silva, Ricardo L.L.; Barreto, Aline; Goto, Hiro; Almeida, Roque P.; Salvatori, Roberto; Aguiar-Oliveira, Manuel H.; Jesus, Amélia M.R.

In: Frontiers in Cellular and Infection Microbiology, Vol. 9, No. AUG, 311, 01.01.2019.

Research output: Contribution to journalArticle

Barrios, MR, Campos, VC, Peres, NTA, de Oliveira, LL, Cazzaniga, RA, Santos, MB, Aires, MB, Silva, RLL, Barreto, A, Goto, H, Almeida, RP, Salvatori, R, Aguiar-Oliveira, MH & Jesus, AMR 2019, 'Macrophages from subjects with isolated GH/IGF-I deficiency due to a ghrh receptor gene mutation are less prone to infection by Leishmania amazonensis', Frontiers in Cellular and Infection Microbiology, vol. 9, no. AUG, 311. https://doi.org/10.3389/fcimb.2019.00311
Barrios, Mônica R. ; Campos, Viviane C. ; Peres, Nalu T.A. ; de Oliveira, Laís L. ; Cazzaniga, Rodrigo A. ; Santos, Márcio B. ; Aires, Murilo B. ; Silva, Ricardo L.L. ; Barreto, Aline ; Goto, Hiro ; Almeida, Roque P. ; Salvatori, Roberto ; Aguiar-Oliveira, Manuel H. ; Jesus, Amélia M.R. / Macrophages from subjects with isolated GH/IGF-I deficiency due to a ghrh receptor gene mutation are less prone to infection by Leishmania amazonensis. In: Frontiers in Cellular and Infection Microbiology. 2019 ; Vol. 9, No. AUG.
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abstract = "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 mouse 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 less prone 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.",
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AU - Peres, Nalu T.A.

AU - de Oliveira, Laís L.

AU - Cazzaniga, Rodrigo A.

AU - Santos, Márcio B.

AU - Aires, Murilo B.

AU - Silva, Ricardo L.L.

AU - Barreto, Aline

AU - Goto, Hiro

AU - Almeida, Roque P.

AU - Salvatori, Roberto

AU - Aguiar-Oliveira, Manuel H.

AU - Jesus, Amélia M.R.

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AB - 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 mouse 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 less prone 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.

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