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自噬受HIV-1感染者维生素D水平的影响。

Autophagy is influenced by vitamin D level in people with HIV-1.

作者信息

Casetti Rita, Ciccosanti Fabiola, Lamsira Harpreet Kaur, Pinnetti Carmela, Mazzotta Valentina, Ciolfi Serena, Sacchi Alessandra, Amendola Alessandra, Ippolito Giuseppe, Piacentini Mauro, Nardacci Roberta

机构信息

Department of Epidemiology, Preclinical Research and Advanced Diagnostics, National Institute for Infectious Diseases 'Lazzaro Spallanzani' - IRCCS, Rome, 00149, Italy.

Departmental Faculty of Medicine, Saint Camillus International University of Health Sciences, Rome, 00131, Italy.

出版信息

Biol Direct. 2025 Jun 13;20(1):69. doi: 10.1186/s13062-025-00660-9.

Abstract

BACKGROUND

Autophagy is the primary catabolic process responsible for degrading intracellular components and potentially harmful cytosolic entities by delivering them to lysosomes. Notably, this mechanism is crucial for controlling intracellular pathogens, with significant implications for both innate and adaptive immunity. In the context of HIV-1 infection, emerging evidence suggests that autophagy contributes to immune responses against the virus. Various compounds can modulate autophagy, among which vitamin D₃ is particularly effective due to its ability to prevent inflammation and slow HIV-1 disease progression. Indeed, vitamin D₃ contributes to regulating both innate and adaptive immunity, thereby modulating antiviral and antibacterial inflammatory responses. Importantly, vitamin D₃ deficiency is highly prevalent among people with HIV (PWH) and has been associated with an increased risk of severe disease progression.

RESULTS

In this study, we investigated the relationship between serum vitamin D₃ levels and the expression of autophagy markers in peripheral blood mononuclear cells from different categories of PWH: PWH under antiretroviral therapy (ART) with either normal vitamin D₃ levels or hypovitaminosis, and treatment-naïve PWH with either normal vitamin D₃ levels or hypovitaminosis. Our results show that low vitamin D₃ blood levels is associated with lower expression of the main factors involved in the autophagy mechanism, particularly in treatment-naïve PWH.

CONCLUSIONS

Our findings suggest that normal blood level of vitamin D₃ may play a crucial role in promoting autophagy in PWH. The observed differences in autophagy-related protein expression between ART-treated and untreated individuals underscore the intricate relationship between vitamin D₃ levels, ART exposure, and autophagic regulation. This is a preliminary exploration of the effects of vitamin D₃ on autophagy in PWH. Further studies are needed to deepen and explore the interplay between vitamin D₃ and autophagy in greater depth. A better understanding of these mechanisms could help to develop novel therapeutic strategies aimed at mitigating immune depletion and chronic inflammation, ultimately improving clinical outcomes for individuals living with HIV.

摘要

背景

自噬是主要的分解代谢过程,负责通过将细胞内成分和潜在有害的胞质实体输送到溶酶体来降解它们。值得注意的是,这种机制对于控制细胞内病原体至关重要,对先天免疫和适应性免疫都有重要影响。在HIV-1感染的背景下,新出现的证据表明自噬有助于针对该病毒的免疫反应。各种化合物可以调节自噬,其中维生素D₃因其能够预防炎症和减缓HIV-1疾病进展而特别有效。事实上,维生素D₃有助于调节先天免疫和适应性免疫,从而调节抗病毒和抗菌炎症反应。重要的是,维生素D₃缺乏在HIV感染者(PWH)中非常普遍,并且与严重疾病进展风险增加有关。

结果

在本研究中,我们调查了不同类别PWH外周血单核细胞中血清维生素D₃水平与自噬标志物表达之间的关系:接受抗逆转录病毒治疗(ART)且维生素D₃水平正常或维生素缺乏的PWH,以及未经治疗且维生素D₃水平正常或维生素缺乏的初治PWH。我们的结果表明,血液中维生素D₃水平低与自噬机制中主要因素的表达降低有关,特别是在初治PWH中。

结论

我们的研究结果表明,正常血液水平的维生素D₃可能在促进PWH的自噬中起关键作用。在接受ART治疗和未治疗的个体之间观察到的自噬相关蛋白表达差异强调了维生素D₃水平、ART暴露和自噬调节之间的复杂关系。这是对维生素D₃对PWH自噬影响的初步探索。需要进一步研究以更深入地探讨维生素D₃与自噬之间的相互作用。更好地理解这些机制有助于开发旨在减轻免疫耗竭和慢性炎症的新治疗策略,最终改善HIV感染者的临床结局。

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