Macrophages From Subjects With Isolated GH/IGF-I Deficiency Due to a GHRH Receptor Gene Mutation Are Less Prone to Infection by Leishmania amazonensis
Macrophages From Subjects With Isolated GH/IGF-I Deficiency Due to a GHRH Receptor Gene Mutation Are Less Prone to Infection by Leishmania amazonensis
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DOI：
10.3389/fcimb.2019.00311
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发表时间：
2019-08-30
影响因子：
5.7
通讯作者：
Jesus, Amelia M. R.
中科院分区：
文献类型：
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作者：
Barrios, Monica R.;Campos, Viviane C.;Jesus, Amelia M. R.
孤立性生长激素(GH)缺乏症(IGHD)影响全球约1/4,000至1/10,000人。我们之前已经描述了由于生长激素释放激素(GHRH)受体基因的纯合子突变而导致的大量IGHD患者。这些受试者一生中生长激素及其主要介体胰岛素生长因子-I(IGF-I)的水平非常低。IGF-I在不同利什曼原虫株感染小鼠巨噬细胞中的促进作用是众所周知的。然而，IGF-I在利什曼原虫感染人巨噬细胞中的作用尚未被研究。本研究旨在评估未经治疗的IGHD患者巨噬细胞体外感染利什曼原虫的行为。为此，采集了14名IGHD患者和14名年龄和性别匹配的健康对照的血液样本。分离单核细胞，扩增成巨噬细胞，感染一株亚马逊利什曼原虫。此外，在培养基中添加IGF-I，以评价其对感染的影响。测定培养上清液中的细胞因子。我们发现，与生长激素充足的对照组相比，IGHD患者的巨噬细胞不太容易感染利什曼原虫。炎症和抗炎细胞因子只在对照巨噬细胞的上清中增加。在培养基中添加IGF-I可增加感染率。综上所述，我们证明了IGF-I在利什曼原虫感染人巨噬细胞过程中起关键作用。
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.