Host Immune Responses in HIV-1 Infection: The Emerging Pathogenic Role of Siglecs and Their Clinical Correlates.
Host Immune Responses in HIV-1 Infection: The Emerging Pathogenic Role of Siglecs and Their Clinical Correlates.
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DOI：
10.3389/fimmu.2017.00314
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发表时间：
2017
影响因子：
7.3
通讯作者：
Mavilio D
中科院分区：
文献类型：
--
作者：
Mikulak J;Di Vito C;Zaghi E;Mavilio D
更好地了解HIV-1逃避免疫反应的机制仍然是开发针对仍然缺乏明确治愈方法的疾病的新治疗方法所需的主要任务之一。宿主对HIV-1的先天免疫反应是感染早期阶段的关键，因为它们可以防止感染的两个标志的发展和建立：慢性炎症和病毒储库。唾液酸结合免疫球蛋白样凝集素（Siglecs）属于跨膜蛋白家族，其能够抑制宿主免疫应答，并在与其天然配体（唾液酸化碳水化合物）连接时设定适当的免疫活化阈值。这种免疫调节功能也是许多病原体的目标，这些病原体已经进化到在其表面表达唾液酸以逃避宿主免疫反应。HIV-1包膜糖蛋白120（gp 120）被广泛的糖类所覆盖，在病毒的生命周期中起着重要的作用。事实上，除了形成抗体识别的保护屏障外，这种N-连接聚糖的外壳干扰病毒糖蛋白的折叠并增强病毒的感染性。特别地，存在于gp 120上的唾液酸残基可以结合自然杀伤细胞和单核细胞/巨噬细胞上的Siglec-7以及单核细胞/巨噬细胞和树突细胞上的Siglec-1。Siglec家族的这两个成员与HIV-1包膜上存在的唾液酸化聚糖之间的相互作用诱导或增加HIV-1进入常规和非常规靶细胞，从而促进病毒传播和疾病进展。在这篇综述中，我们将讨论Siglecs在HIV-1感染发病机制中的作用，并讨论它们如何作为临床和治疗靶点。
A better understanding of the mechanisms employed by HIV-1 to escape immune responses still represents one of the major tasks required for the development of novel therapeutic approaches targeting a disease still lacking a definitive cure. Host innate immune responses against HIV-1 are key in the early phases of the infection as they could prevent the development and the establishment of two hallmarks of the infection: chronic inflammation and viral reservoirs. Sialic acid-binding immunoglobulin-like lectins (Siglecs) belong to a family of transmembrane proteins able to dampen host immune responses and set appropriate immune activation thresholds upon ligation with their natural ligands, the sialylated carbohydrates. This immune-modulatory function is also targeted by many pathogens that have evolved to express sialic acids on their surface in order to escape host immune responses. HIV-1 envelope glycoprotein 120 (gp120) is extensively covered by carbohydrates playing active roles in life cycle of the virus. Indeed, besides forming a protecting shield from antibody recognition, this coat of N-linked glycans interferes with the folding of viral glycoproteins and enhances virus infectivity. In particular, the sialic acid residues present on gp120 can bind Siglec-7 on natural killer and monocytes/macrophages and Siglec-1 on monocytes/macrophages and dendritic cells. The interactions between these two members of the Siglec family and the sialylated glycans present on HIV-1 envelope either induce or increase HIV-1 entry in conventional and unconventional target cells, thus contributing to viral dissemination and disease progression. In this review, we address the impact of Siglecs in the pathogenesis of HIV-1 infection and discuss how they could be employed as clinic and therapeutic targets.