Department of Animal Production and Health, Public Health and Food Science and Technology, Veterinary Medicine Faculty, Facultad de Veterinaria, Universidad Cardenal Herrera-CEU, CEU Universities, Valencia, Spain.
Precision Medicine Unit, INCLIVA Biomedical Research Institute, Valencia, Spain.
Infect Dis Poverty. 2023 Feb 10;12(1):9. doi: 10.1186/s40249-023-01058-3.
The Ibizan Hound is a canine breed native to the Mediterranean region, where leishmaniasis is an endemic zoonosis. Several studies indicate a low prevalence of this disease in Ibizan Hound dogs, whereas other canine breeds present a high prevalence. However, the underlying molecular mechanisms still remain unknown. The aim of this work is to analyse the relationship between serum levels of cytokines and the genomic profiles in two canine breeds, Ibizan Hound (resistant canine breed model) and Boxer (susceptible canine breed model).
In this study, we analyse the haplotypes of genes encoding cytokines related to immune response of Leishmania infantum infection in twenty-four Boxers and twenty-eight Ibizan Hounds apparently healthy using CanineHD DNA Analysis BeadChip including 165,480 mapped positions. The haplo.glm extension of haplo.score was used to perform a General Linear Model (GLM) regression to estimate the magnitude of individual haplotype effects within each cytokine.
Mean levels of interferon gamma (IFN-γ), interleukin 2 (IL-2) and IL-18 in Boxer dogs were 0.19 ± 0.05 ng/ml, 46.70 ± 4.54 ng/ml, and 36.37 ± 30.59 pg/ml, whereas Ibizan Hound dogs present 0.49 ± 0.05 ng/ml, 64.55 ± 4.54 ng/ml, and 492.10 ± 31.18 pg/ml, respectively. The GLM regression shows fifteen haplotypes with statistically significant effect on the cytokine serum levels (P < 0.05). The more relevant are IL6-CGAAG and IFNG-GCA haplotypes, which increase and decrease the IL-2, IL-8 and IFN-γ serum levels, respectively.
Haplotypes in the IFNG and IL6 genes have been correlated to serum levels of IFN-γ, IL-2 and IL-18, and a moderate effect has been found on IL8 haplotype correlated to IL-8 and IL-18 serum levels. The results indicate that the resistance to L. infantum infection could be a consequence of certain haplotypes with a high frequency in the Ibizan Hound dog breed, while susceptibility to the disease would be related to other specific haplotypes, with high frequency in Boxer. Future studies are needed to elucidate whether these differences and haplotypes are related to different phenotypes in immune response and expression gene regulation to L. infantum infections in dogs and their possible application in new treatments and vaccines.
伊比赞猎犬是一种原产于地中海地区的犬种，那里利什曼病是地方性的人畜共患病。几项研究表明，这种疾病在伊比赞猎犬中的发病率较低，而其他犬种的发病率较高。然而，潜在的分子机制仍不清楚。本研究的目的是分析两种犬种（伊比赞猎犬（抗性犬种模型）和拳击手犬（易感犬种模型））的细胞因子血清水平与基因组图谱之间的关系。
在这项研究中，我们使用 CanineHD DNA Analysis BeadChip 分析了 24 只拳击手犬和 28 只伊比赞猎犬中与利什曼原虫感染免疫反应相关的细胞因子基因的单倍型，该芯片包括 165480 个映射位置。使用 haplo.glm 扩展的 haplo.score 执行一般线性模型（GLM）回归，以估计每个细胞因子中单个单倍型效应的大小。
拳击手犬的干扰素γ（IFN-γ）、白细胞介素 2（IL-2）和白细胞介素 18（IL-18）的平均水平分别为 0.19±0.05ng/ml、46.70±4.54ng/ml 和 36.37±30.59pg/ml，而伊比赞猎犬犬的相应水平分别为 0.49±0.05ng/ml、64.55±4.54ng/ml 和 492.10±31.18pg/ml。GLM 回归显示，有 15 个单倍型对细胞因子血清水平有统计学意义（P<0.05）。更相关的是 IL6-CGAAG 和 IFNG-GCA 单倍型，它们分别增加和减少 IL-2、IL-8 和 IFN-γ 的血清水平。
IFNG 和 IL6 基因中的单倍型与 IFN-γ、IL-2 和 IL-18 的血清水平相关，并且在与 IL-8 和 IL-18 血清水平相关的 IL8 单倍型中发现了中等效应。结果表明，对利什曼原虫感染的抗性可能是伊比赞猎犬犬种中某些高频单倍型的结果，而对疾病的易感性则与其他特定的单倍型有关，这些单倍型在拳击手犬中的频率较高。需要进一步的研究来阐明这些差异和单倍型是否与犬类对利什曼原虫感染的免疫反应和基因表达调控的不同表型有关，以及它们在新的治疗方法和疫苗中的可能应用。
