Malaria-specific antibody responses and parasite persistence after infection of mice with Plasmodium chabaudi chabaudi
Malaria-specific antibody responses and parasite persistence after infection of mice with Plasmodium chabaudi chabaudi
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DOI：
10.1111/j.1365-3024.2007.00960.x
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发表时间：
2007-09-01
影响因子：
2.2
通讯作者：
Langhorne, J.
中科院分区：
文献类型：
--
作者：
Achtman, A. H.;Stephens, R.;Langhorne, J.
虽然众所周知抗体对于清除疟疾感染至关重要，但尚不清楚是否能维持足够的抗体反应以及慢性感染对此反应有何影响。在这里，我们发现，与无寄生虫小鼠的第二次感染相比，患有低度慢性查鲍迪疟原虫初次感染或最近消除感染的小鼠的第二次感染减少了。我们还发现，小鼠感染恰鲍迪疟原虫后诱导的寄生虫特异性抗体反应包含短寿命和长寿命成分，以及记忆 B 细胞，它们在再次感染期间负责更快的抗体反应。此外，裂殖子表面蛋白 1 (MSP-1) C 端片段的寄生虫特异性抗体会经历亲合力成熟。然而，具有低亲和力和高亲和力的抗体在整个感染过程中以及再次感染后持续存在，这表明记忆 B 细胞经历了反复的激活和成熟。抗体反应的亲和力特征及其维持都不受持续存在的活寄生虫的影响。因此，再次感染时寄生虫血症的差异不能仅用较高水平的抗体或疟疾特异性抗体的较大亲和力成熟来解释。这些数据表明，对于慢性感染小鼠的继发感染的早期控制，可能存在一种不依赖于抗体的成分。
While it is known that antibodies are critical for clearance of malaria infections, it is not clear whether adequate antibody responses are maintained and what effect chronic infection has on this response. Here we show that mice with low-grade chronic primary infections of Plasmodium chabaudi or infections very recently eliminated have reduced second infections when compared with the second infection of parasite-free mice. We also show that parasite-specific antibody responses induced by infection of mice with Plasmodium chabaudi contain both short- and long-lived components as well as memory B cells responsible for a faster antibody response during re-infection. Furthermore, parasite-specific antibodies to the C-terminal fragment of merozoite surface protein-1 (MSP-1) undergo avidity maturation. However, antibodies with both low and high avidity persist throughout infection and after re-infection, suggesting repeated rounds of activation and maturation of memory B cells. Neither the avidity profile of the antibody response, nor its maintenance is affected by persisting live parasites. Therefore, differences in parasitemia in re-infection cannot be explained solely by higher levels of antibody or greater affinity maturation of malaria-specific antibodies. These data suggest that there may be an antibody-independent component to the early control of secondary infections in mice that are chronically infected.