Ritter Uwe, Körner Heinrich
Nikolaus-Fiebiger Zentrum für Molekulare Medizin, University of Erlangen-Nürnberg, Erlangen, Germany.
Parasite Immunol. 2002 Jun;24(6):295-301. doi: 10.1046/j.1365-3024.2002.00467.x.
Human leishmaniasis is caused by protozoan Leishmania (L.) parasites and comprises a heterogeneous group of clinical appearances ranging from visceral to cutaneous leishmaniasis. In the New World, L. mexicana mediates American cutaneous leishmaniasis, one of the most common forms of this disease. Two different disease progressions can be observed: (i) self-healing localized cutaneous leishmaniasis (LCL) and (ii) progressive diffuse cutaneous leishmaniasis (DCL). These different forms are associated with a T helper 1 (Th1) or Th2 response, respectively, and are additionally characterized by opposing dermal chemokine profiles. Lesions of LCL show high expression of CCL2/MCP-1, CXCL9/MIG, CXCL10/IP-10 and only low amounts of CCL3/MIP-1alpha. In contrast, lesions of chronic DCL are dominated by the expression of CCL3/MIP-1alpha. This finding implies that CCL2/MCP-1 contributes to the healing process. Indeed, CCL2/MCP-1 induces leishmanicidal activities in human monocytes in contrast to CCL3/MIP-1alpha. This effect is enhanced by interferon-gamma and abrogated by interleukin-4. In the murine model of leishmaniasis, the impact of CCL2/MCP-1 is well documented. Normally resistant mice become susceptible for Leishmania infections if CCR2, the receptor for CCL2/MCP-1, is knocked out. Based on this evidence, we propose that tissue specific expression of these small molecules actively regulates cell traffic and tissue localization of effector cells and, additionally, has direct immunological effects.
人类利什曼病由原生动物利什曼原虫（Leishmania，L.）寄生虫引起，临床表现多种多样，从内脏利什曼病到皮肤利什曼病不等。在新大陆，墨西哥利什曼原虫（L. mexicana）引发美洲皮肤利什曼病，这是该疾病最常见的形式之一。可观察到两种不同的疾病进展情况：（i）自愈性局限性皮肤利什曼病（LCL）和（ii）进行性弥漫性皮肤利什曼病（DCL）。这些不同形式分别与辅助性T细胞1（Th1）或Th2反应相关，此外还具有相反的真皮趋化因子谱特征。LCL病变显示CCL2/MCP - 1、CXCL9/MIG、CXCL10/IP - 10高表达，而CCL3/MIP - 1α含量较低。相比之下，慢性DCL病变以CCL3/MIP - 1α的表达为主。这一发现表明CCL2/MCP - 1有助于愈合过程。实际上，与CCL3/MIP - 1α相比，CCL2/MCP - 1可诱导人类单核细胞产生杀利什曼原虫活性。干扰素 - γ可增强这一效应，而白细胞介素 - 4可消除这一效应。在利什曼病的小鼠模型中，CCL2/MCP - 1的影响已有充分记录。如果敲除CCL2/MCP - 1的受体CCR2，正常情况下具有抗性的小鼠会变得易患利什曼原虫感染。基于这些证据，我们提出这些小分子的组织特异性表达可积极调节效应细胞的细胞运输和组织定位，此外还具有直接的免疫效应。
