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曼氏血吸虫和疟疾混合感染在学龄儿童中的严重程度可能受宿主 CD14 基因变异的调节。

Severity of Schistosoma haematobium co-infection with malaria in school-children is potentially modulated by host CD14 gene variants.

机构信息

Department of Biomedical Sciences, Rochester Institute of Technology, 153 Lomb Memorial Drive, Rochester, NY, 14623, USA.

Department of Medical Microbiology and Parasitology, Ladoke Akintola University of Technology, Ogbomosho, Nigeria.

出版信息

BMC Res Notes. 2023 Sep 8;16(1):199. doi: 10.1186/s13104-023-06479-9.

Abstract

OBJECTIVE

Schistosomiasis remains a chronic disease of global importance, especially in many rural areas of the world where co-infection with Plasmodium falciparum is common. It is critical to decipher the role of single or co-infected disease scenarios on immune system regulation in such individuals and how such co-infections can either ameliorate or complicate immune response and the consequent disease outcome. First, 10 ml of urine samples, collected between 10:00 am and 2:00 pm, was filtered for diagnosis of schistosomiasis, while egg count, indicative of disease severity, was determined by microscopy. Furthermore, genomic DNA samples extracted from dried blood spots collected on filter paper from one hundred and forty-four Schistosoma haematobium-infected school-children was tested for P. falciparum parasite positivity by an allele-specific nested-PCR analysis of merozoite surface protein (msp)-1 and -2 genes and a real-time PCR assay. In addition, among P. falciparum parasite-positive individuals, we carried out a Taqman SNP genotyping assay to extrapolate the effect of host CD14 (-159 C/T; rs2569190) genetic variants on schistosome egg count.

RESULTS

Of the 144 individuals recruited, P. falciparum parasite positivity with msp-1 gene were 34%, 43% and 55% for MAD20, RO33 and K1 alleles respectively. Of the co-infected individuals, CD14 genetic variants ranged from 18.8% vs 21.5%, 33.3% vs 44.4%, 9.7% vs 11.8% for single versus schistosome co-infection for the wild type (CC), heterozygous (CT) and mutant (TT) variants respectively. Though the mean egg count for co-infected individuals with CD14 wild type (33.7 eggs per 10 ml of urine) and heterozygote variants (37.5 eggs per 10 ml of urine) were lower than that of schistosome infection alone (52.48 and 48.08 eggs/10 ml of urine respectively), it lacked statistical significance (p-value 0.12 and 0.29), possibly reflecting the benefit of the CD14 activation in schistosome plus malaria co-infection and not schistosome infection alone. In addition, the lower mean egg count in co-infected individuals reveal the benefit of downstream Th1 immune response mitigated by CD14 innate activation that is absent in schistosome infection alone.

摘要

目的

血吸虫病仍然是一种具有全球重要性的慢性疾病,特别是在世界上许多农村地区,那里经常同时感染疟原虫恶性疟原虫。了解单一或合并感染疾病对这些个体的免疫系统调节的作用,以及这种合并感染如何改善或复杂化免疫反应和随后的疾病结果至关重要。首先,采集 10ml 上午 10 点至下午 2 点之间的尿液样本进行血吸虫病诊断,通过显微镜检查确定卵计数,以指示疾病严重程度。此外,从 144 名感染埃及血吸虫的学龄儿童的滤纸上采集的干血斑基因组 DNA 样本,通过等位基因特异性巢式 PCR 分析裂殖体表面蛋白(msp)-1 和 -2 基因以及实时 PCR 检测分析,检测疟原虫寄生虫阳性。此外,在疟原虫寄生虫阳性个体中,我们进行 Taqman SNP 基因分型检测,以推断宿主 CD14(-159C/T;rs2569190)遗传变异对血吸虫卵计数的影响。

结果

在所招募的 144 名个体中,MAD20、RO33 和 K1 等位基因的 msp-1 基因阳性率分别为 34%、43%和 55%。在合并感染的个体中,CD14 遗传变异的范围分别为 18.8%对 21.5%、33.3%对 44.4%、9.7%对 11.8%,对野生型(CC)、杂合型(CT)和突变型(TT)变异体而言,分别为单一感染与血吸虫合并感染。虽然 CD14 野生型(33.7 个/10ml 尿液)和杂合型(37.5 个/10ml 尿液)合并感染个体的平均卵计数低于单纯血吸虫感染(分别为 52.48 和 48.08 个/10ml 尿液),但差异无统计学意义(p 值分别为 0.12 和 0.29),这可能反映了 CD14 激活在血吸虫和疟疾合并感染中的益处,而不是单纯血吸虫感染中的益处。此外,合并感染个体的平均卵计数较低,表明 CD14 先天激活减轻了下游 Th1 免疫反应,而单纯血吸虫感染则不存在这种情况。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4f1d/10486024/967caa39cb40/13104_2023_6479_Fig1_HTML.jpg

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