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 Rueda; Campos, Viviane C.; Peres, Nalu T. A.; Oliveira, Laís Lima de; Cazzaniga, Rodrigo Anselmo; Santos, Márcio Bezerra; Aires, Murilo Buenos; Silva, Ricardo L. L. da; Barreto, Aline Silva; Goto, Hiro; Almeida, Roque Pacheco de; Salvatori, Roberto; Aguiar‐Oliveira, Manuel H.; Jesus, Amélia Ribeiro de

doi:10.3389/fcimb.2019.00311

Cited by 11 publications

(10 citation statements)

References 31 publications

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“…In another study, macrophages from growth hormone (GH)/IGF-I-deficient individuals, due to the growth hormone-releasing hormone receptor gene mutation, were assayed in vitro for L. amazonensis infection. It was observed that the macrophages isolated from these individuals were less prone to infection than healthy control macrophages [ 90 ]. These data certainly confirmed the role of intrinsic IGF-I in intracellular parasite growth.…”

Section: Igf-i In Experimental Leishmaniasismentioning

confidence: 99%

Pleiotropic Effect of Hormone Insulin-Like Growth Factor-I in Immune Response and Pathogenesis in Leishmaniases

Reis

Ramos-Sanchez

Araújo

et al. 2021

Journal of Immunology Research

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Leishmaniases are diseases caused by several Leishmania species, and many factors contribute to the development of the infection. Because the adaptive immune response does not fully explain the outcome of Leishmania infection and considering that the initial events are crucial in the establishment of the infection, we investigated one of the growth factors, the insulin-like growth factor-I (IGF-I), found in circulation and produced by different cells including macrophages and present in the skin where the parasite is inoculated. Here, we review the role of IGF-I in leishmaniasis experimental models and human patients. IGF-I induces the growth of different Leishmania species in vitro and alters the disease outcome increasing the parasite load and lesion size, especially in L. major- and L. amazonensis-infected mouse leishmaniasis. IGF-I affects the parasite interacting with the IGF-I receptor present on Leishmania. During Leishmania-macrophage interaction, IGF-I acts on the arginine metabolic pathway, resulting in polyamine production both in macrophages and Leishmania. IGF-I and cytokines interact with reciprocal influences on their expression. IL-4 is a hallmark of susceptibility to L. major in murine leishmaniasis, but we observed that IGF-I operates astoundingly as an effector element of the IL-4. Approaching human leishmaniasis, patients with mucosal, disseminated, and visceral diseases presented surprisingly low IGF-I serum levels, suggesting diverse effects than parasite growth. We observed that low IGF-I levels might contribute to the inflammatory response persistence and delayed lesion healing in human cutaneous leishmaniasis and the anemia development in visceral leishmaniasis. We must highlight the complexity of infection revealed depending on the Leishmania species and the parasite’s developmental stages. Because IGF-I exerts pleiotropic effects on the biology of interaction and disease pathogenesis, IGF-I turns up as an attractive tool to explore biological and pathogenic processes underlying infection development. IGF-I pleiotropic effects open further the possibility of approaching IGF-I as a therapeutical target.

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Section: Igf-i In Experimental Leishmaniasismentioning

confidence: 99%

Pleiotropic Effect of Hormone Insulin-Like Growth Factor-I in Immune Response and Pathogenesis in Leishmaniases

Reis

Ramos-Sanchez

Araújo

et al. 2021

Journal of Immunology Research

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“…The changes in GLP-1 secretion and postprandial ghrelin levels detected in IGHD subjects from this cohort were viewed as favorable [ 73 ]. Interestingly, macrophages from subjects with the Itabaianinha syndrome were less prone to infection by Leishmania amazonensis [ 74 ]. This appears to be related to reduced circulating IGF-I levels in these individuals, because adding IGF-I to the medium increased the infection rate [ 74 ].…”

Section: Novel Findings In Individuals With Growth Hormone Deficiency or Growth Hormone Resistancementioning

confidence: 99%

“…Interestingly, macrophages from subjects with the Itabaianinha syndrome were less prone to infection by Leishmania amazonensis [ 74 ]. This appears to be related to reduced circulating IGF-I levels in these individuals, because adding IGF-I to the medium increased the infection rate [ 74 ]. The picture that emerges from these and previous studies by the group of Prof. Aguiar-Oliveira is that severe (but not complete) suppression of GH secretion in these subjects leads to multiple functional changes, some of which are beneficial and some detrimental, with the beneficial effects prevailing in terms of the apparent extension of health span and reduced risk of age-related chronic disease [ 31 65 75 ].…”

Section: Novel Findings In Individuals With Growth Hormone Deficiency or Growth Hormone Resistancementioning

confidence: 99%

“…However, GH was also reported to have pro-inflammatory effects by promoting cell senescence and secretion of pro-inflammatory cytokines while reducing the secretion of anti-inflammatory adiponectin [ 26 , 27 , 28 , 83 ]. IGHD was reported to protect from Leishmania infection [ 74 ]. Apparently, GH has divergent effects on different aspects of immune function, inflammation, and responses to infection.…”

Section: Can Growth Hormone Reverse Aging?mentioning

confidence: 99%

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Growth Hormone and Aging: New Findings

Bartke

Hascup

et al. 2021

World J Mens Health

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Complex relationships between growth hormone (GH) signaling and mammalian aging continue to attract attention of many investigators. Recent results include evidence that the impact of GH on genome maintenance (DNA damage and repair) is drastically different in normal as compared to cancer cells, consistent with GH promoting aging and cancer progression. Impact of GH on DNA methylation was studied as a possible mechanism linking actions of GH during early life to the trajectory of aging. Animals with reduced or enhanced GH signaling and novel animals with adipocyte-specific deletion of GH receptors were used to elucidate the effects of GH on white and brown adipose tissue, including the impact of this hormone on lipolysis, fibrosis, and thermogenesis. Effects of GH on adipose tissue related to lipid and energy metabolism emerge as mechanistic links between GH, healthspan, and lifespan. Treatment of healthy men with a combination of GH, dehydroepiandrosterone, and metformin was reported to restore thymus function and reduce epigenetic age. Studies of human subjects with deficiency of GH or GH receptors and studies of mice with the same endocrine syndromes identified several phenotypic changes related (positively or negatively) to the previously reported predisposition to healthy aging. Results of these and other recent studies advance present understanding of the mechanisms by which GH influences aging and longevity and of the trade-offs involved.

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“…A Brazilian population of individuals with isolated GH deficiency (IGHD) due to a mutation of the GHRH receptor gene, studied by Aguiar-Oliveira and his colleagues, exhibit numerous features of “healthy aging” including reduced risk of atherosclerosis, improved insulin sensitivity, reduced fatigue, and retention of hair pigmentation ( 38 ). In addition, subjects affected by IGHD in this cohort appear to be resistant to infections by an endemic parasite, Leishmania ( 61 ), and to cope better with Covid-19 infections ( 62 ). However, these characteristics appear to have little, if any, impact on their longevity ( 38 ).…”

Section: Introductionmentioning

confidence: 96%

Somatotropic Axis, Pace of Life and Aging

Bartke

2022

Front. Endocrinol.

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Mice with genetic growth hormone (GH) deficiency or GH resistance live much longer than their normal siblings maintained under identical conditions with unlimited access to food. Extended longevity of these mutants is associated with extension of their healthspan (period of life free of disability and disease) and with delayed and/or slower aging. Importantly, GH and GH-related traits have been linked to the regulation of aging and longevity also in mice that have not been genetically altered and in other mammalian species including humans. Avai+lable evidence indicates that the impact of suppressed GH signaling on aging is mediated by multiple interacting mechanisms and involves trade-offs among growth, reproduction, and longevity. Life history traits of long-lived GH-related mutants include slow postnatal growth, delayed sexual maturation, and reduced fecundity (smaller litter size and increased intervals between the litters). These traits are consistent with a slower pace-of-life, a well-documented characteristic of species of wild animals that are long-lived in their natural environment. Apparently, slower pace-of-life (or at least some of its features) is associated with extended longevity both within and between species. This association is unexpected and may appear counterintuitive, because the relationships between adult body size (a GH-dependent trait) and longevity within and between species are opposite rather than similar. Studies of energy metabolism and nutrient-dependent signaling pathways at different stages of the life course will be needed to elucidate mechanisms of these relationships.

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Macrophages From Subjects With Isolated GH/IGF-I Deficiency Due to a GHRH Receptor Gene Mutation Are Less Prone to Infection by Leishmania amazonensis

Cited by 11 publications

References 31 publications

Pleiotropic Effect of Hormone Insulin-Like Growth Factor-I in Immune Response and Pathogenesis in Leishmaniases

Pleiotropic Effect of Hormone Insulin-Like Growth Factor-I in Immune Response and Pathogenesis in Leishmaniases

Growth Hormone and Aging: New Findings

Somatotropic Axis, Pace of Life and Aging

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