Mathematical and Statistical Computing Laboratory, Division of Computational Bioscience, Center for Information Technology, National Institutes of Health, Bethesda, Maryland, USA.
Malar J. 2013 Jun 15;12:206. doi: 10.1186/1475-2875-12-206.
Plasmodium infections trigger complex immune reactions from their hosts against several life stages of the parasite, including gametocytes. These immune responses are highly variable, depending on age, genetics, and exposure history of the host as well as species and strain of parasite. Although the effects of host antibodies that act against gamete stages in the mosquito (due to uptake in the blood meal) are well documented, the effects of host immunity upon within-host gametocytes are not as well understood. This report consists of a theoretical population biology-based analysis to determine constraints that host immunity impose upon gametocyte population growth. The details of the mathematical models used for the analysis were guided by published reports of clinical and animal studies, incorporated plausible modalities of immune reactions to parasites, and were tailored to the life cycl es of the two most widespread human malaria pathogens, Plasmodium falciparum and Plasmodium vivax.
For the same ability to bind and clear a target, the model simulations suggest that an antibody attacking immature gametocytes would tend to lower the overall density of transmissible mature gametocytes more than an antibody attacking the mature forms directly. Transmission of P. falciparum would be especially vulnerable to complete blocking by antibodies to its immature forms since its gametocytes take much longer to reach maturity than those of P. vivax. On the other hand, antibodies attacking the mature gametocytes directly would reduce the time the mature forms can linger in the host. Simulation results also suggest that varying the standard deviation in the time necessary for individual asexual parasites to develop and produce schizonts can affect the efficiency of production of transmissible gametocytes.
If mature gametocyte density determines the probability of transmission, both Plasmodium species, but especially P. falciparum, could bolster this probability through evasion or suppression of host immune responses against the immature gametocytes. However, if the long term lingering of mature gametocytes at low density in the host is also important to ensure transmission, then evasion or suppression of antibodies against the mature stages would bolster probability of transmission as well.
疟原虫感染会引发宿主针对寄生虫多个生命阶段（包括配子体）的复杂免疫反应。这些免疫反应具有高度变异性，取决于宿主的年龄、遗传背景、暴露史以及寄生虫的种类和株系。尽管宿主抗体在蚊媒中针对配子体阶段（由于在血餐中摄取）的作用效果已有充分的文献记载，但宿主免疫对体内配子体的影响却尚未得到充分理解。本报告包含基于理论种群生物学的分析，以确定宿主免疫对配子体种群增长的制约因素。分析中所使用的数学模型的细节是根据临床和动物研究的已发表报告指导的，纳入了对寄生虫免疫反应的合理模式，并针对两种最广泛传播的人类疟疾病原体，恶性疟原虫和间日疟原虫的生命周期进行了调整。
在具有相同结合和清除靶标能力的情况下，模型模拟表明，攻击未成熟配子体的抗体往往比直接攻击成熟形式的抗体更能降低可传播的成熟配子体的总体密度。抗体完全阻断恶性疟原虫不成熟形式的传播能力尤其脆弱，因为其配子体达到成熟所需的时间比间日疟原虫长得多。另一方面，直接攻击成熟配子体的抗体将减少成熟形式在宿主体内逗留的时间。模拟结果还表明，改变单个无性寄生虫发育和产生裂殖体所需的时间的标准差可以影响可传播配子体的产生效率。
如果成熟配子体的密度决定了传播的概率，那么这两种疟原虫（尤其是恶性疟原虫）都可以通过逃避或抑制宿主针对未成熟配子体的免疫反应来增加这种概率。然而，如果成熟配子体在宿主体内低浓度长期存在对于确保传播也很重要，那么逃避或抑制针对成熟阶段的抗体也会增加传播的概率。
