"Autoimmune rejection" of neonatal heart transplants in experimental Chagas disease is a parasite-specific response to infected host tissue.
"Autoimmune rejection" of neonatal heart transplants in experimental Chagas disease is a parasite-specific response to infected host tissue.
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实验性恰加斯病中新生儿心脏移植的“自身免疫排斥”是寄生虫对受感染宿主组织的特异性反应。
DOI：
10.1073/pnas.94.8.3932
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发表时间：
1997
影响因子：
11.1
通讯作者：
Downs,MO
中科院分区：
文献类型：
--
作者：
Tarleton,RL;Zhang,L;Downs,MO
感染原生动物寄生虫克氏斑虫通常会导致慢性心脏和肠道相关疾病，即恰加斯病。在这项研究中，我们表明，与以往的报道相反，新生儿心脏移植到慢性感染t的小鼠。克鲁齐多没有表现出自身免疫性排斥反应或任何明显的炎症反应。除了没有炎症外，这些同基因心脏移植存活超过1年，并且通过原位upcr分析确定绝对没有寄生虫。然而，如果在慢性感染小鼠的移植心脏中直接注射活寄生虫，则会产生迅速而剧烈的炎症反应，导致心脏功能停止。同样，移植心脏在全身感染t病毒之前在小鼠体内建立。急性期心脏移植到小鼠体内。克鲁兹感染被寄生并发展为炎症灶。在这些移植的心脏被寄生的情况下，随后的炎症反应几乎与在原生心脏中观察到的相同。克鲁兹感染小鼠在细胞类型和粘附分子及细胞因子表达方面的差异。重要的是，这种反应与异体心脏排斥反应截然不同。这些结果清楚地证明，心脏组织的寄生是诱发恰加斯病组织损伤的必要和充分条件，并强烈反对这种疾病的主要自身免疫性病因。
Infection with the protozoan parasiteTrypanosoma cruzioften results in chronic heart- and gut-associated disease known as Chagas disease. In this study we show that contrary to previous reports, neonatal hearts transplanted into mice chronically infected withT. cruzido not exhibit signs of autoimmune-type rejection or any significant inflammatory response. In addition to an absence of inflammation, these syngeneic heart transplants survive for more than 1 year and are absolutely free of parasites as determined byin situPCR analysis. However, if well-established transplanted hearts in chronically infected mice are directly injected with live parasites, a rapid and dramatic inflammatory response ensues that results in cessation of heart function. Likewise, transplanted hearts established in mice prior to systemic infection withT. cruzior hearts transplanted into mice during the acute stage ofT. cruziinfection become parasitized and develop inflammatory foci. In these cases where the transplanted hearts become parasitized, the ensuing inflammatory response is nearly identical to that observed in the native hearts ofT. cruzi-infected mice in terms of cell types present and adhesion molecules and cytokines expressed. Importantly, this response is strikingly different from that observed in the allogeneic heart rejection. These results clearly document that parasitization of heart tissue is both necessary and sufficient for the induction of tissue damage in Chagas disease and strongly argue against a principal autoimmune etiology for this disease.