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Contrasting behavior between the three human monocyte subsets in dengue pathophysiology.

ABSTRACT: Monocytes are known to play a critical role in dengue pathophysiology. However, which monocyte subset expresses what inflammatory mediator(s) and what transcriptional features distinguish each of the monocyte subset in vivo remain poorly understood. In this study we provide a detailed transcriptional analysis of the three human monocyte subsets in healthy children and in children with dengue febrile illness. Notably, we found that the CD14⁺ CD16high intermediate monocyte subset from dengue patients highly upregulated key genes involved in mediating inflammation, endothelial dysfunction, vascular permeability, tissue extravasation, and clot prevention compared to healthy children. The CD14⁺CD16low classical monocytes shared some of these features. These two subsets increased massively in patients with severe dengue. By contrast, the CD14^-CD16high nonclassical monocyte subset upregulated key genes involved in vasoconstriction, endothelial barrier stability, and are involved in endothelial patrolling while showing a significant decline from circulation. These findings improve our understanding of monocyte responses in dengue.

SUBMITTER: Maheshwari D

PROVIDER: S-EPMC9127603 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature

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Contrasting behavior between the three human monocyte subsets in dengue pathophysiology.

Maheshwari Deepti D Saini Keshav K Saini Keshav K Singh Prabhat P Singla Mohit M Nayak Kaustuv K Aggarwal Charu C Chawla Yadya M YM Bajpai Prashant P Kaur Manpreet M Gunisetty Sivaram S Eberhardt Christiane S CS Nyodu Rajni R Moore Kathryn K Suthar Mehul S MS Medigeshi Guruprasad R GR Anderson Evan E Lodha Rakesh R Kabra Sushil K SK Ahmed Rafi R Chandele Anmol A Murali-Krishna Kaja K

iScience 20220510 6

Monocytes are known to play a critical role in dengue pathophysiology. However, which monocyte subset expresses what inflammatory mediator(s) and what transcriptional features distinguish each of the monocyte subset <i>in vivo</i> remain poorly understood. In this study we provide a detailed transcriptional analysis of the three human monocyte subsets in healthy children and in children with dengue febrile illness. Notably, we found that the CD14<sup>+</sup> CD16high intermediate monocyte subset ...[more]

PMID: 35620424

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Project description:BackgroundAge-associated changes in immunity are inextricably linked to chronic inflammation and age-related diseases, the impact of aging on monocyte subsets is poorly understood.MethodsFlow cytometry was applied to distinguish three monocyte subsets between 120 young and 103 aged individuals. We then analyzed the expression profiles of three monocyte subsets from 9 young and 9 older donors and CD14+ monocytes from 1202 individuals between 44 and 83 years old. Flow cytometry was used to measure β-galactosidase activities, ROS levels, mitochondrial contents, mitochondrial membrane potentials (MMPs) and intracellular IL-6 levels in three monocyte subsets of young and elderly individuals, and plasma IL-6 levels were detected by electrochemiluminescence immunoassay. Mitochondrial stress and glycolytic rate of CD14+ monocytes from young and aged individuals were measured by Seahorse XFe24 Analyzer.ResultsCompared with young individuals, the percentage of classical subset in aged persons significantly decreased, while the proportion of nonclassical subset increased. Age-related differential genes were obviously enriched in cellular senescence, ROS, oxidative phosphorylation, mitochondrial respiratory chain, IL-6 and ribosome-related pathways. Compared with young individuals, the β-galactosidase activities, ROS contents, intracellular IL-6 levels of three monocyte subsets, and plasma IL-6 levels in aged individuals were significantly elevated, while the MMPs apparently declined with age and the mitochondrial contents were only increased in intermediate and nonclassical subsets. CD14+ monocytes from elderly adults had conspicuously lower basal and spare respiratory capacity and higher basal glycolysis than those from young individuals.ConclusionsDuring aging, monocytes exhibited senescence-associated secretory phenotype, mitochondrial dysfunction, decreased oxidative phosphorylation and increased glycolysis and the nonclassical subset displayed the clearest features of aging. Our study comprehensively investigated age-related transcriptional alterations of three monocyte subsets and identified the pivotal pathways of monocyte senescence, which may have significant implications for tactics to alleviate age-related conditions.

Dataset Information

Contrasting behavior between the three human monocyte subsets in dengue pathophysiology.

Publications

Contrasting behavior between the three human monocyte subsets in dengue pathophysiology.

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