Immunoregulatory role of MΦ/DCs in the liver of murine malaria infected mice

我们已经报道了NKT细胞的一个亚群，称为CD3^&lt；int&gt；IL-2Rβ+NK1.1-亚群，在感染P.yoelli 17XNL的C57BL/6(B6)小鼠的肝脏中扩增，有助于预防疟疾。另一方面，我们的研究结果表明，在疟疾感染后，肝脏树突状细胞(DC)可能通过激活肝脏NKT细胞而在调节免疫反应中发挥重要作用。然而，这一方法还没有得到明确的阐明。本研究试图分析疟疾感染小鼠肝脏树突状细胞的表型和功能。树突状细胞分为髓系树突状细胞(MDC)和浆细胞样树突状细胞(PDC)。小鼠肝脏在体外经CpG刺激产生干扰素-α的PDCA-1+CD11c；lt；low&gt；I-A-B220+DC绝对数较高。脾组织中以PDCA-1-CD11c、HIGH、I-A+B220-DC(MDC)为主。两种表型的DC均能产生IL-12、IL-10和肿瘤坏死因子α。从疟疾感染者…中分离到的CD11c^&lt；low&A-DC急性期(7日龄)小鼠肝、脾组织明显增多。CD86高表达，PDCA-1表达减少，干扰素-α产生减少。从感染小鼠分离的I-A-CD11c；Low&gt；DC与MDCS相比，细胞因子的产生受到抑制。在疟疾感染恢复期(25天后)，肝、脾CD11c、Low、Gt；I-A组分中的PDCA-1~+细胞重新出现。这些结果表明，MDCS通过细胞因子激活NKT细胞，而激活的NKT细胞促进了疟疾感染小鼠的保护活性和疾病症状。PDC通过抑制干扰素-α的产生而产生免疫抑制效应。目的(由M-Φ表达的凋亡抑制因子)缺陷小鼠缺乏部分M-Φ和DC功能，并且被发现比B6小鼠从疟疾感染中恢复得更快。γδT细胞在肝脏和脾组织中大量增殖，尤其是在恢复期。这些发现清楚地显示了肝脏DC的表型和功能变化，并可能支持肝脏DC对疟疾感染后肝脏NKT细胞功能的调节。较少

We have already reported that one subset of NKT cells, known as CD3^<int>IL-2Rβ+NK1.1-subset, expanded in the liver of P.yoelli 17XNL-infected C57BL/6(B6) mice and contributed to protection against malaria. On the other hand, accumulating results of our studies suggested that liver dendritic cells (DCs) might play a critical role in the regulation of immune responses through activation of liver NKT cells after malarial infection. However, this approach has not been clearly elucidated. In this study we attempted to analyze the phenotype and function of liver DCs in malaria infected mice.DCs are classified into two majour subpopulations ; myeloid DC (mDC) and plasmacytoid DC (pDC). Murine liver had high absolute number of PDCA-1+CD11c^<low>I-A-B220+DC (pDC) which produced IFN-α by stimulation with CpG in vitro. PDCA-1-CD11c^<high>I-A+B220-DC (mDC) were dominant in the spleen. DCs of both phenotypes were able to produce IL-12, IL-10 and TNFα. CD11c^<low>I-A-DC isolated from malaria infect … More ed mice increased in the liver and spleen at acute phase (7 days). These cells showed high expression of CD86 but decreased PDCA-1 expression and IFN-α production. I-A-CD11c^<low>DCs isolated from infected mice showed impaired production of cytokines as compared with mDCs. PDCA-1^+ cells in CD11c^<low>I-A- fraction of liver and spleen reappeared at recovery phase (after 25 days) of malarial infection. These results indicate that while mDCs activate NKT cells via cytokines and that activated NKT cells promote the protective activity and disease syndromes in malaria infected mice. pDCs induce the immunosuppressive effects due to impaired production of IFN-α. AIM (apoptosis inhibitor expressed by MΦ) deficient mice lack some of MΦ and DC functions and were found to recover more quickly from malarial infection than B6 mice. γδT cells expanded in the liver and spleen, especially in the recovery phase. These findings clearly showed the phenotypical and functional change of DCs in the liver and may support the view that liver DC regulate the function of NKT cells in the liver after malarial infection. Less