LOCALIZATION OF MAJOR HISTOCOMPATIBILITY COMPLEX CLASS-II MOLECULES IN PHAGOLYSOSOMES OF MURINE MACROPHAGES INFECTED WITH LEISHMANIA-AMAZONENSIS
LOCALIZATION OF MAJOR HISTOCOMPATIBILITY COMPLEX CLASS-II MOLECULES IN PHAGOLYSOSOMES OF MURINE MACROPHAGES INFECTED WITH LEISHMANIA-AMAZONENSIS
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DOI：
10.1128/iai.59.3.764-775.1991
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发表时间：
1991-03-01
影响因子：
3.1
通讯作者：
FREHEL, C
中科院分区：
文献类型：
--
作者：
ANTOINE, JC;JOUANNE, C;FREHEL, C
利什曼原虫感染的巨噬细胞是CD 4 + T淋巴细胞的潜在抗原呈递细胞，其识别与主要组织相容性复合物II类分子（Ia）结合的寄生虫抗原。然而，Ia和抗原可能相互作用的细胞内位点远不清楚，因为寄生虫在宿主细胞的修饰的溶酶体隔室内生长，而Ia分子似乎靶向于内体。为了解决这个问题，Ia分子的表达和命运进行了研究，免疫细胞化学在亚马逊利什曼原虫感染的小鼠巨噬细胞刺激γ干扰素。在未感染的巨噬细胞中，Ia分子定位于质膜和核周囊泡中，但它们在感染后经历了戏剧性的重新分布，因为大多数细胞内染色随后与寄生虫空泡（p. v.）并且常常朝向无鞭毛体结合位点极化。Ii不变链，这是短暂的Ia在其细胞内运输，虽然在感染的巨噬细胞表达良好，显然没有达到p. v.类似的结果观察到与巨噬细胞从小鼠抗或高度易感利什曼原虫感染。为了确定p. v.的来源-与Ia相关，在感染后测定用特异性抗体检测的质膜、内体和溶酶体标志物的命运。在感染后48小时，发现p. v.表现出典型的成熟溶酶体的膜组成。总体而言，这些数据表明（i）位于p. v.中的Ia来源于参与该隔室生物发生的次级溶酶体或在几种内吞细胞器（包括溶酶体）中循环，以及（ii）p. v.可能在抗原加工和呈递中发挥作用。或者，在p. v.中存在大量Ia可能是由于利什曼原虫诱导的机制，通过该机制，该生物体可能逃避免疫应答。
Leishmania-infected macrophages are potential antigen-presenting cells for CD4+ T lymphocytes, which recognize parasite antigens bound to major histocompatibility complex class II molecules (Ia). However, the intracellular sites where Ia and antigens may interact are far from clear, since parasites grow within the modified lysosomal compartment of the host cell, whereas Ia molecules seem to be targeted to endosomes. To address this question, the expression and fate of Ia molecules were studied by immunocytochemistry in Leishmania amazonensis-infected murine macrophages stimulated with gamma interferon. In uninfected macrophages, Ia molecules were localized on the plasma membrane and in perinuclear vesicles, but they underwent a dramatic redistribution after infection, since most of the intracellular staining was then associated with the periphery of the parasitophorous vacuoles (p.v.) and quite often polarized towards amastigote-binding sites. The Ii invariant chain, which is transiently associated with Ia during their intracellular transport, although well expressed in infected macrophages, apparently did not reach the p.v. Similar findings were observed with macrophages from mice either resistant or highly susceptible to Leishmania infection. In order to determine the origin of p.v.-associated Ia, the fate of plasma membrane, endosomal, and lysosomal markers, detected with specific antibodies, was determined after infection. At 48 h after infection, p.v. was found to exhibit a membrane composition typical of mature lysosomes. Overall, these data suggest that (i) Ia located in p.v. originate from secondary lysosomes involved in the biogenesis of this compartment or circulate in several endocytic organelles, including lysosomes and (ii) p.v. could play a role in antigen processing and presentation. Alternatively, the presence of high amounts of Ia in p.v. could be due to a Leishmania-induced mechanism by means of which this organism may evade the immune response.