Human intestinal macrophages display profound inflammatory anergy despite avid phagocytic and bacteriocidal activity
Human intestinal macrophages display profound inflammatory anergy despite avid phagocytic and bacteriocidal activity
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DOI：
10.1172/jci200519229
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发表时间：
2005-01-01
影响因子：
15.9
通讯作者：
Smith, PD
中科院分区：
文献类型：
--
作者：
Smythies, LE;Sellers, M;Smith, PD
肠巨噬细胞，这被认为是协调粘膜炎症反应，已收到很少的研究关注相比，从其他组织的巨噬细胞。在这里，我们表明，人类肠道巨噬细胞不表达先天性反应受体，包括LPS（CD 14），Fcalpha（CD 89），Fc γ（CD 64，CD 32，CD 16），CR 3（CD 11b/CD 18）和CR 4（CD 11 c/CD 18）的受体;生长因子受体IL-2（CD 25）和IL-3（CD 123）;和整合素LFA-1（CD 11 a/CD 18）。此外，常驻肠道巨噬细胞也不会响应一系列炎症刺激而产生促炎细胞因子，包括IL-1、IL-6、IL-10、IL-12、RANTES、TGF-β和TNF-α，但保留了旺盛的吞噬和杀菌活性。因此，尽管肠巨噬细胞来源于血液单核细胞，但肠巨噬细胞在表型和功能上与血液单核细胞明显不同。为了解释这一矛盾，我们表明，肠道基质细胞衍生的产品下调单核细胞受体的表达，并通过TGF-β，细胞因子的产生，但不吞噬或杀菌活性，引起的表型和功能的肠巨噬细胞。这些发现表明了一种机制，其中招募到肠粘膜的血液单核细胞保留了贪婪的清道夫和宿主防御功能，但获得了深刻的“炎症无反应性”，从而促进了正常肠粘膜的炎症特征的缺乏，尽管免疫刺激性细菌非常接近。
Intestinal macrophages, which are thought to orchestrate mucosal inflammatory responses, have received little investigative attention compared with macrophages from other tissues. Here we show that human intestinal macrophages do not express innate response receptors, including the receptors for LPS (CD14), Fcalpha (CD89), Fcgamma (CD64, CD32, CD16), CR3 (CD11b/CD18), and CR4 (CD11c/CD18); the growth factor receptors IL-2 (CD25) and IL-3 (CD123); and the integrin LFA-1 (CD11a/CD18). Moreover, resident intestinal macrophages also do not produce proinflammatory cytokines, including IL-1, IL-6, IL-10, IL-12, RANTES, TGF-beta, and TNF-alpha, in response to an array of inflammatory stimuli but retain avid phagocytic and bacteriocidal activity. Thus, intestinal macrophages are markedly distinct in phenotype and function from blood monocytes, although intestinal macrophages are derived from blood monocytes. To explain this paradox, we show that intestinal stromal cell-derived products downregulate both monocyte receptor expression and, via TGF-beta, cytokine production but not phagocytic or bacteriocidal activity, eliciting the phenotype and functional profile of intestinal macrophages. These findings indicate a mechanism in which blood monocytes recruited to the intestinal mucosa retain avid scavenger and host defense functions but acquire profound "inflammatory anergy," thereby promoting the absence of inflammation characteristic of normal intestinal mucosa despite the close proximity of immunostimulatory bacteria.