Mycobacterium tuberculosis Coinfection Has No Impact on Plasmodium berghei ANKA-Induced Experimental Cerebral Malaria in C57BL/6 Mice
Mycobacterium tuberculosis Coinfection Has No Impact on Plasmodium berghei ANKA-Induced Experimental Cerebral Malaria in C57BL/6 Mice
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DOI：
10.1128/iai.01290-15
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发表时间：
2016-02-01
影响因子：
3.1
通讯作者：
Schneider, Bianca E.
中科院分区：
文献类型：
--
作者：
Blank, Jannike;Behrends, Jochen;Schneider, Bianca E.
脑型疟疾（CM）是人类感染恶性疟原虫最严重的并发症。诱发CM的机制仍未完全了解。促炎免疫反应是控制血期疟疾感染所必需的，但也与CM的发病机制有关。为了在不诱导宿主病理的情况下清除寄生虫，需要在促炎性和抗炎性免疫反应之间取得良好的平衡。最被接受的研究人类CM的实验模型是C57BL/6小鼠的伯氏疟原虫ANKA （PbANKA）感染，导致复杂的神经综合征的发展，与人类疾病有许多共同的特征。我们应用该模型研究了先前感染结核分枝杆菌（结核的病原体）的小鼠感染PbANKA的结果。在热带大片地区，结核病与疟疾共流行，据报道，分枝杆菌在实验性共感染模型中对啮齿动物疟原虫具有一定程度的非特异性保护作用。我们发现合并结核分枝杆菌感染并未改变pbanka诱导C57BL/6小鼠实验性脑型疟疾（ECM）的临床病程。单独感染和合并感染的小鼠脾脏和大脑的免疫环境没有差异；相反，共感染小鼠的总体细胞因子和T细胞反应与单独感染PbANKA的小鼠相当。我们的数据表明结核分枝杆菌合并感染不能改变pbanka诱导的疾病的结果，很可能是因为寄生虫诱导的炎症反应在先前感染结核分枝杆菌的小鼠中迅速占主导地位。
Cerebral malaria (CM) is the most severe complication of human infection with Plasmodium falciparum. The mechanisms predisposing to CM are still not fully understood. Proinflammatory immune responses are required for the control of blood-stage malaria infection but are also implicated in the pathogenesis of CM. A fine balance between pro-and anti-inflammatory immune responses is required for parasite clearance without the induction of host pathology. The most accepted experimental model to study human CM is Plasmodium berghei ANKA (PbANKA) infection in C57BL/6 mice that leads to the development of a complex neurological syndrome which shares many characteristics with the human disease. We applied this model to study the outcome of PbANKA infection in mice previously infected with Mycobacterium tuberculosis, the causative agent of tuberculosis. Tuberculosis is coendemic with malaria in large regions in the tropics, and mycobacteria have been reported to confer some degree of unspecific protection against rodent Plasmodium parasites in experimental coinfection models. We found that concomitant M. tuberculosis infection did not change the clinical course of PbANKA-induced experimental cerebral malaria (ECM) in C57BL/6 mice. The immunological environments in spleen and brain did not differ between singly infected and coinfected animals; instead, the overall cytokine and T cell responses in coinfected mice were comparable to those in animals solely infected with PbANKA. Our data suggest that M. tuberculosis coinfection is not able to change the outcome of PbANKA-induced disease, most likely because the inflammatory response induced by the parasite rapidly dominates in mice previously infected with M. tuberculosis.