Bourgeois Christine, Gorwood Jennifer, Barrail-Tran Aurélie, Lagathu Claire, Capeau Jacqueline, Desjardins Delphine, Le Grand Roger, Damouche Abderaouf, Béréziat Véronique, Lambotte Olivier
Center for Immunology of Viral Infections and Autoimmune Diseases, IDMIT Department, IBFJ, CEA, Université Paris Sud, INSERM U1184, Fontenay-aux-Roses, France.
INSERM UMR_S 938, Centre de Recherche Saint-Antoine, Institut Hospitalo-Universitaire de Cardio-Métabolisme et Nutrition (ICAN), Sorbonne Université, Paris, France.
Front Microbiol. 2019 Dec 17;10:2837. doi: 10.3389/fmicb.2019.02837. eCollection 2019.
Although white AT can contribute to anti-infectious immune responses, it can also be targeted and perturbed by pathogens. The AT's immune involvement is primarily due to strong pro-inflammatory responses (with both local and paracrine effects), and the large number of fat-resident macrophages. Adipocytes also exert direct antimicrobial responses. In recent years, it has been found that memory T cells accumulate in AT, where they provide efficient secondary responses against viral pathogens. These observations have prompted researchers to re-evaluate the links between obesity and susceptibility to infections. In contrast, AT serves as a reservoir for several persistence pathogens, such as human adenovirus Ad-36, , , influenza A virus, and cytomegalovirus (CMV). The presence and persistence of bacterial DNA in AT has led to the concept of a tissue-specific microbiota. The unexpected coexistence of immune cells and pathogens within the specific AT environment is intriguing, and its impact on anti-infectious immune responses requires further evaluation. AT has been recently identified as a site of HIV persistence. In the context of HIV infection, AT is targeted by both the virus and the antiretroviral drugs. AT's intrinsic metabolic features, large overall mass, and wide distribution make it a major tissue reservoir, and one that may contribute to the pathophysiology of chronic HIV infections. Here, we review the immune, metabolic, viral, and pharmacological aspects that contribute to HIV persistence in AT. We also evaluate the respective impacts of both intrinsic and HIV-induced factors on AT's involvement as a viral reservoir. Lastly, we examine the potential consequences of HIV persistence on the metabolic and immune activities of AT.
虽然白色脂肪组织可促进抗感染免疫反应,但病原体也可将其作为攻击目标并对其造成干扰。脂肪组织的免疫参与主要归因于强烈的促炎反应(具有局部和旁分泌作用)以及大量驻留脂肪的巨噬细胞。脂肪细胞也发挥直接的抗菌反应。近年来,人们发现记忆T细胞在脂肪组织中积聚,在那里它们针对病毒病原体提供有效的二次免疫反应。这些观察结果促使研究人员重新评估肥胖与感染易感性之间的联系。相比之下,脂肪组织是几种持续性病原体的储存库,如人腺病毒Ad - 36、甲型流感病毒和巨细胞病毒(CMV)。脂肪组织中细菌DNA的存在和持续存在导致了组织特异性微生物群概念的产生。免疫细胞和病原体在特定脂肪组织环境中的意外共存令人着迷,其对抗感染免疫反应的影响需要进一步评估。脂肪组织最近被确定为HIV持续存在的一个部位。在HIV感染的背景下,脂肪组织既是病毒的攻击目标,也是抗逆转录病毒药物的作用靶点。脂肪组织固有的代谢特征、总体积大以及分布广泛,使其成为一个主要的组织储存库,并且可能促成慢性HIV感染的病理生理学过程。在此,我们综述了导致HIV在脂肪组织中持续存在的免疫、代谢、病毒和药理学方面。我们还评估了内在因素和HIV诱导因素对脂肪组织作为病毒储存库参与情况的各自影响。最后,我们研究了HIV持续存在对脂肪组织代谢和免疫活动的潜在后果。