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CD 3 + <int>IL-2 R β+NK1.1-亚群，在约氏疟原虫17 XNL感染的C57 BL/6（B6）小鼠的肝脏中扩增，并有助于预防疟疾。另一方面，我们的研究积累的结果表明，肝脏树突状细胞（DC）可能通过激活肝脏NKT细胞在疟疾感染后的免疫反应的调节中发挥关键作用。然而，这一方法尚未得到明确阐明。本研究试图分析疟疾感染小鼠肝脏DC的表型和功能，DC分为两个主要亚群：髓样DC（myeloid DC，mDC）和浆细胞样DC（plasmacytoid DC，pDC）。小鼠肝脏中PDCA-1+ CD 11 c ^<low>I-A-B220+DC（pDC）的绝对数量较高，经CpG体外刺激可产生IFN-α。脾脏中以PDCA-1-CD 11 c、<high>I-A+B220-DC（mDC）为主。两种表型的DC均能产生IL-12、IL-10和TNFα。从<low>疟疾感染中分离的CD 11 c ^ I-A-DC 关于我们 艾德小鼠在急性期（7天）肝脏和脾脏中增加。这些细胞显示出高表达CD 86，但降低PDCA-1表达和IFN-α产生。与<low>mDC相比，从感染小鼠分离的I-A-CD 11 c ^DC显示细胞因子的产生受损。在<low>疟疾感染的恢复期（25天后），肝脏和脾脏的CD 11 c ^ I-A-组分中的PDCA-1^+细胞再次出现。这些结果表明，虽然mDCs通过细胞因子激活NKT细胞，但激活的NKT细胞促进了疟疾感染小鼠的保护活性和疾病综合征。pDC由于IFN-α的产生受损而诱导免疫抑制作用。AIM（MΦ表达的凋亡抑制剂）缺陷小鼠缺乏MΦ和DC的某些功能，并且发现从疟疾感染中恢复比B6小鼠更快。γδT细胞在肝脏和脾脏中扩增，特别是在恢复期。这些结果清楚地显示了DC在肝脏中的表型和功能变化，并可能支持了疟疾感染后肝脏DC调节肝脏NKT细胞功能的观点。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