A systemic granulomatous response to Schistosoma mansoni eggs alters responsiveness of bone marrow-derived macrophages to Toll-like receptor agonists
A systemic granulomatous response to Schistosoma mansoni eggs alters responsiveness of bone marrow-derived macrophages to Toll-like receptor agonists
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DOI：
10.1189/jlb.1007689
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发表时间：
2008-02-01
影响因子：
5.5
通讯作者：
Hogaboam, Cory M.
中科院分区：
文献类型：
--
作者：
Joshi, Amrita D.;Raymond, Tracy;Hogaboam, Cory M.
巨噬细胞在曼氏血吸虫的先天性和获得性免疫应答中起着关键作用。这些细胞的经典（M1）或替代（M2）激活状态进一步描述了它们分别通过先天免疫或纤维化重塑在组织损伤中的作用。在本研究中，我们解决了以下问题：是否系统性Th 2型细胞因子极化诱发的S。mansoni影响巨噬细胞的分化和活化？为此，我们分析了来自S. mansoni卵诱导的肺肉芽肿和未攻击的（或幼稚的）小鼠，以确定它们的活化状态和它们对特异性TLR激动剂（包括S.曼氏虫卵抗原与幼稚巨噬细胞不同，来自Th 2极化小鼠的巨噬细胞组成性表达显著更高的“在炎症区-1中发现”（FIZZ 1）和ST 2（M2标记物），并且显著降低NO合酶2、CCL 3、MIP-2、TNF-α和IL-12（M1标记物）。此外，与幼稚巨噬细胞相比，Th 2极化的巨噬细胞对特异性TLR激动剂的存在表现出增强的反应，这始终诱导这些细胞中M2和M1标志物的基因和蛋白水平显著更高。总之，这些数据表明，在S。曼氏虫卵诱导的肉芽肿反应动态地改变巨噬细胞的发育并增强这些细胞的TLR反应性，这最终可能对肺肉芽肿反应具有显著影响。
Macrophages play a pivotal role in innate and acquired immune responses to Schistosoma mansoni. Classical (M1) or alternative (M2) activation states of these cells further delineate their roles in tissue damage through innate immunity or fibrotic remodeling, respectively. In the present study, we addressed the following question: Does systemic Th2-type cytokine polarization evoked by S. mansoni affect macrophage differentiation and activation? To this end, we analyzed bone marrow-derived macrophages from mice with S. mansoni egg-induced pulmonary granulomas and unchallenged (or naive) mice to determine their activation state and their response to specific TLR agonists, including S. mansoni egg antigens. Unlike naive macrophages, macrophages from Th2-polarized mice constitutively expressed significantly higher "found in inflammatory zone-1" (FIZZ1) and ST2 (M2 markers) and significantly lower NO synthase 2, CCL3, MIP-2, TNF-alpha, and IL-12 (M1 markers). Also, compared with naive macrophages, Th2-polarized macrophages exhibited enhanced responses to the presence of specific TLR agonists, which consistently induced significantly higher levels of gene and protein levels for M2 and M1 markers in these cells. Together, these data show that signals received by bone marrow precursors during S. mansoni egg-induced granuloma responses dynamically alter the development of macrophages and enhance the TLR responsiveness of these cells, which may ultimately have a significant effect on the pulmonary granulomatous response.