دورية أكاديمية
أعرض في EDS

Peripheral blood mononuclear cell transcriptomes reveal an over-representation of down-regulated genes associated with immunity in HIV-exposed uninfected infants.

التفاصيل البيبلوغرافية
العنوان: Peripheral blood mononuclear cell transcriptomes reveal an over-representation of down-regulated genes associated with immunity in HIV-exposed uninfected infants.
المؤلفون: Musimbi ZD; Center of Biotechnology and Bioinformatics, Chiromo Campus, University of Nairobi, Nairobi, Kenya. zanetakidiavai@gmail.com., Rono MK; KEMRI-Wellcome Trust Research Programme, Kilifi, Kenya. MRono@kemri-wellcome.org.; Pwani University Biotechnology Research Centre, Pwani University, Kilifi, Kenya. MRono@kemri-wellcome.org., Otieno JR; KEMRI-Wellcome Trust Research Programme, Kilifi, Kenya., Kibinge N; KEMRI-Wellcome Trust Research Programme, Kilifi, Kenya., Ochola-Oyier LI; KEMRI-Wellcome Trust Research Programme, Kilifi, Kenya.; Pwani University Biotechnology Research Centre, Pwani University, Kilifi, Kenya., de Villiers EP; KEMRI-Wellcome Trust Research Programme, Kilifi, Kenya.; Centre for Tropical Medicine and Global Health, University of Oxford, Oxford, UK., Nduati EW; KEMRI-Wellcome Trust Research Programme, Kilifi, Kenya.; Pwani University Biotechnology Research Centre, Pwani University, Kilifi, Kenya.
المصدر: Scientific reports [Sci Rep] 2019 Dec 02; Vol. 9 (1), pp. 18124. Date of Electronic Publication: 2019 Dec 02.
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Nature Publishing Group Country of Publication: England NLM ID: 101563288 Publication Model: Electronic Cited Medium: Internet ISSN: 2045-2322 (Electronic) Linking ISSN: 20452322 NLM ISO Abbreviation: Sci Rep Subsets: MEDLINE
أسماء مطبوعة: Original Publication: London : Nature Publishing Group, copyright 2011-
مواضيع طبية MeSH: HIV Infections/*immunology , HIV Infections/*prevention & control , Immunity, Innate/*genetics , Leukocytes, Mononuclear/*physiology, Antibiotic Prophylaxis ; Case-Control Studies ; Down-Regulation ; Gene Regulatory Networks ; HIV Infections/genetics ; Humans ; Immunity, Maternally-Acquired/genetics ; Infant ; Leukocytes, Mononuclear/parasitology ; Malaria/immunology ; Neutrophils/physiology ; Receptors, CCR10/genetics ; Transcriptome
مستخلص: HIV-exposed uninfected (HEU) infants are disproportionately at a higher risk of morbidity and mortality, as compared to HIV-unexposed uninfected (HUU) infants. Here, we used transcriptional profiling of peripheral blood mononuclear cells to determine immunological signatures of in utero HIV exposure. We identified 262 differentially expressed genes (DEGs) in HEU compared to HUU infants. Weighted gene co-expression network analysis (WGCNA) identified six modules that had significant associations with clinical traits. Functional enrichment analysis on both DEGs and the six significantly associated modules revealed an enrichment of G-protein coupled receptors and the immune system, specifically affecting neutrophil function and antibacterial responses. Additionally, malaria pathogenicity genes (thrombospondin 1-(THBS 1), interleukin 6 (IL6), and arginine decarboxylase 2 (ADC2)) were down-regulated. Of interest, the down-regulated immunity genes were positively correlated to the expression of epigenetic factors of the histone family and high-mobility group protein B2 (HMGB2), suggesting their role in the dysregulation of the HEU transcriptional landscape. Overall, we show that genes primarily associated with neutrophil mediated immunity were repressed in the HEU infants. Our results suggest that this could be a contributing factor to the increased susceptibility to bacterial infections associated with higher morbidity and mortality commonly reported in HEU infants.
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معلومات مُعتمدة: 095068/Z/10/Z United Kingdom WT_ Wellcome Trust; EP-C-15-003 United States EPA EPA; United Kingdom WT_ Wellcome Trust
المشرفين على المادة: 0 (Receptors, CCR10)
تواريخ الأحداث: Date Created: 20191204 Date Completed: 20201217 Latest Revision: 20240205
رمز التحديث: 20240205
مُعرف محوري في PubMed: PMC6889308
DOI: 10.1038/s41598-019-54083-4
PMID: 31792230
قاعدة البيانات: MEDLINE
الوصف
تدمد:2045-2322
DOI:10.1038/s41598-019-54083-4