NKT细胞促进了对登革热病毒的Th1免疫偏差,该偏差控制了长期保护性抗体动态
Youngjoo Choi1, Wilfried Aa Saron1, Aled O'Neill1
1Programme in Emerging Infectious Diseases, Duke-National University of Singapore Medical School, Singapore.
The Journal of clinical investigation
|August 1, 2024
概括
不变的自然杀手T (iNKT) 细胞在登革热病毒感染期间促进Th1免疫力,增强病毒清除和长期保护. 它们的缺失导致免疫偏差,并在随后的感染中增加疾病严重程度.
科学领域:
- 免疫学 免疫学 免疫学
- 病毒学 病毒学
- 传染性疾病 传染性疾病
背景情况:
- 不变的自然杀手T (iNKT) 细胞是具有免疫作用的与生相似的淋巴细胞,但它们对长期病毒记忆的贡献尚未完全理解.
- 由包括iNKT细胞在内的细胞毒性细胞产生的Granzyme K与人类初级登革热病毒 (DENV) 感染期间的Th1抗体诱导有关.
研究的目的:
- 在DENV感染期间实体研究CD1d依赖 (CD1ddep) iNKT细胞在DENV感染期间的作用.
- 确定iNKT细胞功能如何影响免疫记忆的发展以及对同源和异源DENV重新挑战的保护.
主要方法:
- 使用了DENV感染的小鼠,它们的基因缺乏CD1d依赖iNKT细胞 (CD1d-KO小鼠).
- 评估了 Th1/Th2 免疫两极化,病毒清除,以及在初级和二级 DENV 感染后的存活率.
- 使用野生型 (WT) 和IFN-γ-knockout (KO) iNKT细胞的采用转移来评估IFN-γ的作用.
主要成果:
- CD1d-KO小鼠表现出受损的Th1免疫力和延迟的感染解脱,这取决于内在的iNKT细胞产生IFN-γ.
- iNKT细胞缺乏导致对Th2反应 (较高的IgG1/IgG2a比率) 的免疫偏差,危及对同源DENV重新挑战的保护.
- 这种偏差在二次异质感染期间促进了抗体依赖增强的疾病,反映了在人类DENV感染中与Th2倾斜 (较高的IgG4/IgG3比率) 的观察.
结论:
- CD1ddep iNKT细胞对于在早期对DENV的先天反应期间建立Th1极性至关重要.
- 这种Th1两极化促进了有效的感染解决,记忆形成和长期保护,防止同源和异源DENV再感染.
- 早期的先天性免疫反应,特别是iNKT细胞,显著影响二次感染的结果和疾病的严重程度.
相关概念视频
Immune Response Against Viral Pathogens
766
The immune system's response to viral infections is a complex and coordinated process involving natural killer (NK) cells, T cell-mediated responses, and antibody-mediated responses.
NK Cells
NK cells are a crucial part of our innate immune system, acting as the first line of defense against viral infections. These cells can recognize and kill infected cells without prior exposure to the virus, effectively slowing down the spread of infection. Additionally, NK cells produce proinflammatory...
NK Cells
NK cells are a crucial part of our innate immune system, acting as the first line of defense against viral infections. These cells can recognize and kill infected cells without prior exposure to the virus, effectively slowing down the spread of infection. Additionally, NK cells produce proinflammatory...
766
Cytotoxic T Cells-mediated Immune Response
865
Cytotoxic T cells are a vital component of the immune system. They have the remarkable ability to identify and target antigens on infected or abnormal cells. These antigens often originate from intracellular pathogens such as viruses or abnormal proteins cancer cells produce.
Immunological surveillance is the ability of immune cells to monitor and eliminate infected cells with intracellular pathogens, neoplastically transformed cells, and cells with non-self antigens. Cytotoxic T cells and NK...
Immunological surveillance is the ability of immune cells to monitor and eliminate infected cells with intracellular pathogens, neoplastically transformed cells, and cells with non-self antigens. Cytotoxic T cells and NK...
865
Cells of the Adaptive Immune Response
972
The T and B lymphocytes of the adaptive immune system develop from common lymphoid progenitor cells in the bone marrow. These progenitors give rise to precursors that eventually develop into both T and B lymphocytes. As these precursors mature, they gain the ability to detect and respond to foreign antigens in the body, a process known as immunocompetence. Additionally, these precursors acquire self-tolerance, a process that ensures they do not react to self-antigens. This intricate system...
972
Cells of the Innate Immune Response
1.6K
The innate immune response is an immediate and non-specific response against pathogens, acting swiftly to prevent the spread of infections. The primary cells involved in this response are phagocytes and natural killer (NK) cells.
Phagocytes
Phagocytes police the peripheral tissues by removing cellular debris and responding to the invasion of foreign substances or pathogens. Many phagocytes attack and remove microorganisms even before lymphocytes detect them. The human body has two general...
Phagocytes
Phagocytes police the peripheral tissues by removing cellular debris and responding to the invasion of foreign substances or pathogens. Many phagocytes attack and remove microorganisms even before lymphocytes detect them. The human body has two general...
1.6K
Immunological Memory
570
Immunological memory, a pivotal pillar of the adaptive immune system, is responsible for the body's ability to remember and respond more swiftly and effectively to previously encountered pathogens. This remarkable feature is what makes vaccines so effective in preventing diseases.
What is Immunological Memory?
Immunological memory is an integral function of the immune system that allows it to recognize and react more rapidly and effectively to pathogens previously encountered. This feature...
What is Immunological Memory?
Immunological memory is an integral function of the immune system that allows it to recognize and react more rapidly and effectively to pathogens previously encountered. This feature...
570
Immune Surveillance by NK Cells and Phagocytes
1.4K
Immune surveillance is an integral part of the innate immune system, involving the continuous monitoring of peripheral tissues to detect and respond to pathogens, infected cells, or cancerous cells. This surveillance is conducted primarily by natural killer (NK) cells and phagocytes, which employ distinct but complementary mechanisms to identify and eliminate threats.
Natural Killer Cells: The Fast Responders
NK cells are large granular lymphocytes found in the blood and lymphatic system. These...
Natural Killer Cells: The Fast Responders
NK cells are large granular lymphocytes found in the blood and lymphatic system. These...
1.4K


