Plasmodium suppresses expansion of T cell responses to heterologous infections.
Plasmodium suppresses expansion of T cell responses to heterologous infections.
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DOI：
10.4049/jimmunol.1401745
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发表时间：
2015-01-15
期刊：
影响因子：
--
通讯作者：
Schmidt NW
中科院分区：
文献类型：
--
作者：
White CE;Villarino NF;Sloan SS;Ganusov VV;Schmidt NW
疟原虫仍然是导致疟疾和削弱对其他感染的防御的主要病原体。确定疟原虫如何增加对异源病原体的易感性，可能会导致采取干预措施，减轻合并感染的严重程度。先前的研究表明，混合感染期间T细胞反应的减少是由于感染诱导趋化因子CCL21的减少而减少了幼稚T细胞的招募。我们发现，虽然李斯特菌感染降低了小鼠脾中CCL21的表达，但在李斯特菌和LCMV混合感染期间，LCMV特异性T细胞反应并未受到损害，这表明这种趋化因子在联合感染诱导的T细胞抑制中起主要作用。在我们的实验中，约氏疟原虫感染确实导致了CD8+T细胞对随后的李斯特菌感染的反应降低。我们提出了约氏疟原虫抑制李斯特菌特异性T细胞反应的另一种机制。我们发现，在与约氏杆菌混合感染期间，李斯特菌特异的T细胞反应扩张较慢，达到较低的数量。数学模型和实验表明，李斯特菌特异性效应T细胞的高凋亡率是主要机制，因为约氏疟原虫感染并没有抑制李斯特菌特异性T细胞的募集或增殖率。我们的结果表明，约氏疟原虫感染通过导致李斯特菌特异性T细胞凋亡增加而抑制对李斯特菌的免疫，从而导致T细胞反应的扩张率减慢。
Plasmodium remains a major pathogen causing malaria and impairing defense against other infections. Defining how Plasmodium increases susceptibility to heterologous pathogens may lead to interventions that mitigate the severity of coinfections. Previous studies have proposed that reduced T cell responses during coinfections are due to diminished recruitment of naïve T cells through infection-induced decreases in chemokine CCL21. We found that while Listeria infections reduced expression of CCL21 in murine spleens, LCMV-specific T cell responses were not impaired during Listeria+LCMV coinfection, arguing against the major role of this chemokine in coinfection-induced T cell suppression. In our experiments, Plasmodium yoelii infection indeed led to a reduced CD8+ T cell response to a subsequent Listeria infection. We propose an alternative mechanism whereby P. yoelii suppresses Listeria-specific T cell responses. We found that Listeria-specific T cell responses expanded slower and reached lower numbers during coinfection with P. yoelii. Mathematical modeling and experimentation indicate higher apoptosis of Listeria-specific effector T cells as the main mechanism because P. yoelii infections did not suppress the recruitment or proliferation rates of Listeria-specific T cells. Our results suggest that P. yoelii infections suppress immunity to Listeria through causing elevated apoptosis in Listeria-specific T cells resulting in a slower expansion rate of T cell responses.
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DOI：
10.1084/jem.20001021
发表时间：
2002-03-04
期刊：
The Journal of experimental medicine
影响因子：
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Blattman JN;Antia R;Sourdive DJ;Wang X;Kaech SM;Murali-Krishna K;Altman JD;Ahmed R
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10.1084/jem.20050821
发表时间：
2005-09-05
期刊：
The Journal of experimental medicine
影响因子：
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