دورية أكاديمية
Plasmodium falciparum malaria drives epigenetic reprogramming of human monocytes toward a regulatory phenotype.
| العنوان: | Plasmodium falciparum malaria drives epigenetic reprogramming of human monocytes toward a regulatory phenotype. |
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| المؤلفون: | Rajan Guha, Anna Mathioudaki, Safiatou Doumbo, Didier Doumtabe, Jeff Skinner, Gunjan Arora, Shafiuddin Siddiqui, Shanping Li, Kassoum Kayentao, Aissata Ongoiba, Judith Zaugg, Boubacar Traore, Peter D Crompton |
| المصدر: | PLoS Pathogens, Vol 17, Iss 4, p e1009430 (2021) |
| بيانات النشر: | Public Library of Science (PLoS), 2021. |
| سنة النشر: | 2021 |
| المجموعة: | LCC:Immunologic diseases. Allergy LCC:Biology (General) |
| مصطلحات موضوعية: | Immunologic diseases. Allergy, RC581-607, Biology (General), QH301-705.5 |
| الوصف: | In malaria-naïve children and adults, Plasmodium falciparum-infected red blood cells (Pf-iRBCs) trigger fever and other symptoms of systemic inflammation. However, in endemic areas where individuals experience repeated Pf infections over many years, the risk of Pf-iRBC-triggered inflammatory symptoms decreases with cumulative Pf exposure. The molecular mechanisms underlying these clinical observations remain unclear. Age-stratified analyses of uninfected, asymptomatic Malian individuals before the malaria season revealed that monocytes of adults produced lower levels of inflammatory cytokines (IL-1β, IL-6 and TNF) in response to Pf-iRBC stimulation compared to monocytes of Malian children and malaria-naïve U.S. adults. Moreover, monocytes of Malian children produced lower levels of IL-1β and IL-6 following Pf-iRBC stimulation compared to 4-6-month-old infants. Accordingly, monocytes of Malian adults produced more IL-10 and expressed higher levels of the regulatory molecules CD163, CD206, Arginase-1 and TGM2. These observations were recapitulated in an in vitro system of monocyte to macrophage differentiation wherein macrophages re-exposed to Pf-iRBCs exhibited attenuated inflammatory cytokine responses and a corresponding decrease in the epigenetic marker of active gene transcription, H3K4me3, at inflammatory cytokine gene loci. Together these data indicate that Pf induces epigenetic reprogramming of monocytes/macrophages toward a regulatory phenotype that attenuates inflammatory responses during subsequent Pf exposure. Trial Registration: ClinicalTrials.gov NCT01322581. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 1553-7366 1553-7374 |
| العلاقة: | https://doaj.org/toc/1553-7366Test; https://doaj.org/toc/1553-7374Test |
| DOI: | 10.1371/journal.ppat.1009430 |
| الوصول الحر: | https://doaj.org/article/86ed53875a52418bb875339a289caf1cTest |
| رقم الانضمام: | edsdoj.86ed53875a52418bb875339a289caf1c |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 15537366 15537374 |
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| DOI: | 10.1371/journal.ppat.1009430 |