Activation of murine macrophages by Neisseria meningitidis and IFN-γ in vitro:: distinct roles of class A scavenger and toll-like pattern recognition receptors in selective modulation of surface phenotype
Activation of murine macrophages by Neisseria meningitidis and IFN-γ in vitro:: distinct roles of class A scavenger and toll-like pattern recognition receptors in selective modulation of surface phenotype
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DOI：
10.1189/jlb.0104014
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发表时间：
2004-09-01
影响因子：
5.5
通讯作者：
Gordon, S
中科院分区：
文献类型：
--
作者：
Mukhopadhyay, S;Peiser, L;Gordon, S
微生物和抗原激活的淋巴细胞分别对巨噬细胞（Mphi）进行先天性和适应性免疫激活，在宿主防御和免疫病理学中发挥着重要作用。抗原呈递细胞表达一系列模式识别受体，包括 A 类 I 型和 II 型清道夫受体 (SR-A) 和 Toll 样受体 (TLR)。 SR-A 和 TLR 对微生物产物的识别可控制摄取、杀死、改变基因表达和适应性免疫反应；然而，每种受体的贡献以及与干扰素γ（IFN-γ）等细胞因子刺激的相互作用尚未确定。我们使用先天免疫的有效激活剂脑膜炎奈瑟菌 (NM) 和 1 型原型 T 辅助细胞促炎细胞因子 IFN-γ 来比较野生型和转基因小鼠品系引发的腹膜 Mphi 的表面抗原、介质分泌和受体功能。我们发现，这些刺激差异性地调节主要组织相容性复合体 II 型 (MHC-II) 和共刺激分子，以及甘露糖受体和具有胶原结构的 Mphi 受体 (MARCO) 的表达，这是一种独特的 SR-A，为先天激活提供了选择性标记。结合起来，NM 抑制 IFN-γ 对 MHC-II 的上调，同时引发肿瘤坏死因子 α 和一氧化氮的增强释放。 SR-A 有助于生物体的吞噬作用，但不影响其诱导 CD80、CD86 和 MARCO 或抑制 MHC-II 的能力。相反，对脂多糖 (LPS) 缺陷生物体和/或 TLR-4 突变小鼠的研究表明，LPS 和 TLR-4 至少部分需要诱导 CD80、CD86 和 MARCO，但抑制 MHC-II 不需要 LPS。这些研究提供了实验模型并鉴定了用于分析 Mphi 先天性和获得性免疫激活的表面标记。
Innate and adaptive immune activation of macrophages (Mphi) by microorganisms and antigen-activated lymphoid cells, respectively, plays an important role in host defense and immunopathology. Antigen-presenting cells express a range of pattern recognition receptors including the class A types I and II scavenger receptors (SR-A) and Toll-like receptors (TLR). Recognition of microbial products by SR-A and TLR controls uptake, killing, altered gene expression, and the adaptive immune response; however, the contribution of each receptor and interplay with cytokine stimuli such as interferon-gamma (IFN-gamma) are not defined. We used Neisseria meningitidis (NM), a potent activator of innate immunity, and IFN-gamma, a prototypic T helper cell type 1 proinflammatory cytokine, to compare surface antigens, secretion of mediators, and receptor functions in elicited peritoneal Mphi from wild-type and genetically modified mouse strains. We show that these stimuli regulate major histocompatibility complex type II (MHC-II) and costimulatory molecules differentially, as well as expression of the mannose receptor and of Mphi receptor with collagenous structure (MARCO), a distinct SR-A, which provides a selective marker for innate activation. In combination, NM inhibited up-regulation of MHC-II by IFN-gamma while priming enhanced release of tumor necrosis factor alpha and nitric oxide. The SR-A contributes to phagocytosis of the organisms but not to their ability to induce CD80, CD86, and MARCO or to inhibit MHC-II. Conversely, studies with lipopolysaccharide (LPS)-deficient organisms and/or TLR-4 mutant mice showed that LPS and TLR-4 are at least partially required to induce CD80, CD86, and MARCO, but LPS is not required to inhibit MHC-II. These studies provide an experimental model and identify surface markers for analysis of innate and acquired immune activation of Mphi.