Perspective of HLA-G Induced Immunosuppression in SARS-CoV-2 Infection.
Perspective of HLA-G Induced Immunosuppression in SARS-CoV-2 Infection.
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DOI：
10.3389/fimmu.2021.788769
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发表时间：
2021
影响因子：
7.3
通讯作者：
Yan WH
中科院分区：
文献类型：
--
作者：
Lin A;Yan WH
COVID-19是由严重急性呼吸道综合征冠状病毒2（SARS-CoV-2）引起的疾病，已威胁到全球公共卫生。宿主抗病毒免疫应答对于病毒清除和疾病控制至关重要，然而，在COVID-19患者中通常观察到免疫细胞数量显著减少和宿主细胞免疫应答耗尽。这是一个值得关注的问题，因为它与疾病的严重程度和不良结局密切相关。人类白细胞抗原-G（HLA-G）是多种免疫抑制受体的配体，其表达可被病毒感染上调。HLA-G/受体信号传导，例如与免疫球蛋白样转录物2（ILT-2）或ILT-4接合，不仅抑制T和自然杀伤（NK）细胞免疫应答、树突状细胞（DC）成熟和B细胞抗体产生。它还诱导调节细胞，如髓源性抑制细胞（MDSC）或M2型巨噬细胞。此外，HLA-G与CD 8和杀伤抑制受体（KIR）2DL 4的相互作用可引起T细胞凋亡和NK细胞衰老。在这种情况下，HLA-G可以诱导深刻的免疫抑制，这有利于SARS-CoV-2逃避免疫攻击。尽管对HLA-G在SARS-CoV-2感染中的临床相关性的详细了解有限，但我们在此综述了SARS-CoV-2感染中HLA-G/受体信号传导的免疫病理学方面，这可以更好地了解COVID-19疾病进展并确定潜在的免疫干预措施以对抗SARS-CoV-2感染。
COVID-19, the disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has threatened public health worldwide. Host antiviral immune responses are essential for viral clearance and disease control, however, remarkably decreased immune cell numbers and exhaustion of host cellular immune responses are commonly observed in patients with COVID-19. This is of concern as it is closely associated with disease severity and poor outcomes. Human leukocyte antigen-G (HLA-G) is a ligand for multiple immune inhibitory receptors, whose expression can be upregulated by viral infections. HLA-G/receptor signalling, such as engagement with immunoglobulin-like transcript 2 (ILT-2) or ILT-4, not only inhibit T and natural killer (NK) cell immune responses, dendritic cell (DC) maturation, and B cell antibody production. It also induces regulatory cells such as myeloid-derived suppressive cells (MDSCs), or M2 type macrophages. Moreover, HLA-G interaction with CD8 and killer inhibitory receptor (KIR) 2DL4 can provoke T cell apoptosis and NK cell senescence. In this context, HLA-G can induce profound immune suppression, which favours the escape of SARS-CoV-2 from immune attack. Although detailed knowledge on the clinical relevance of HLA-G in SARS-CoV-2 infection is limited, we herein review the immunopathological aspects of HLA-G/receptor signalling in SARS-CoV-2 infection, which could provide a better understanding of COVID-19 disease progression and identify potential immunointerventions to counteract SARS-CoV-2 infection.
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作者：
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