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How does monocyte metabolism impact inflammation and aging during chronic HIV infection?

机译:慢性HIV感染期间单核细胞代谢如何影响炎症和衰老?

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A model: how glucose metabolism in monocyfes influences the development of age-related diseases in HIV+ individuals receiving antiretroviral therapy. HIV infection reduces the integrity of the gut mucos.a allowing bacterial products [e.g., lipopolysaccharide (LPS) and endotoxins] to enter the gut submucosa and cross into the bloodstream. Bacterial products induce monocyte metabolic activation and a concomitant increase in glucose transporter 1 (Glut1) expression, glucose uptake, and glycolysis, predominantly within the intermediate monocyte subpopulation. Intermediate monocytes are key producers of inflammatory mediators [e.g., interleukin (IL)-6 and tumor necrosis factor (TNF)] and are a critical population implicated in chronic inflammation in HIV-infected individuals. Ongoing inflammation increases the risk of age-associated comorbidities and causes premature immune aging. Activation of monocytes also encourages CD11b expression on intermediate monocytes, prompts monocyte transition to macrophages and foam cells, and thereby increases the risk of cardiovascular disease in HIV-infected individuals. Activation of monocytes causes enzymatic shedding of CD14 (sCD14) and CD163 (sCD163) from their plasma membrane. Plasma levels of sCD14 and sCD163 are surrogate markers of immune activation and inflammation. HIV-infected persons on antiretroviral therapy (HIV+/ cART) despite maintaining undetectable viral loads below 50 copies/ml with normal CD4 T cell counts remain at risk of acquiring age-related diseases, including diabetes, cardiovascular disease, kidney failure, neurocognitive decline, osteoporosis, and frailty.
机译:一个模型:单核细胞中的葡萄糖代谢如何影响接受抗逆转录病毒疗法的HIV +个体中与年龄有关的疾病的发展。 HIV感染会降低肠粘膜的完整性,从而使细菌产品[例如脂多糖(LPS)和内毒素]进入肠粘膜下层并进入血液。细菌产品诱导单核细胞代谢活化,并同时增加葡萄糖转运蛋白1(Glut1)的表达,葡萄糖摄取和糖酵解,主要在中间单核细胞亚群内。中间单核细胞是炎症介质的主要生产者[例如,白介素(IL)-6和肿瘤坏死因子(TNF)],并且是与HIV感染者的慢性炎症有关的关键人群。持续的炎症会增加与年龄相关的合并症的风险,并导致免疫早衰。单核细胞的活化还鼓励中间单核细胞上CD11b的表达,促使单核细胞转变为巨噬细胞和泡沫细胞,从而增加了HIV感染者罹患心血管疾病的风险。单核细胞的激活导致CD14(sCD14)和CD163(sCD163)从其质膜中酶促脱落。 sCD14和sCD163的血浆水平是免疫激活和炎症的替代标志。接受抗逆转录病毒治疗(HIV + / cART)的HIV感染者,尽管其病毒载量低于50拷贝/ ml,且CD4 T细胞计数正常,仍存在罹患与年龄有关的疾病的风险,包括糖尿病,心血管疾病,肾衰竭,神经认知功能下降,骨质疏松和虚弱。

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