Experimental manipulation of immune-mediated disease and its fitness costs for rodent malaria parasites.
Experimental manipulation of immune-mediated disease and its fitness costs for rodent malaria parasites.
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DOI：
10.1186/1471-2148-8-128
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发表时间：
2008-04-30
影响因子：
3.4
通讯作者：
Graham AL
中科院分区：
文献类型：
--
作者：
Long GH;Chan BH;Allen JE;Read AF;Graham AL
解释寄生虫的毒力（对宿主的伤害）对进化和生物医学科学家来说都是一个重大挑战。大多数毒力进化的理论模型假设毒力的产生是宿主利用的直接结果，即寄生虫将宿主资源转化为传播机会的过程。然而，感染诱导的疾病可以是免疫介导的（免疫病理学）。关于免疫病理学如何影响寄生虫适应性，或者它将如何影响寄生虫毒力的进化，我们知之甚少。在这里，我们研究了免疫病理学对感染诱导的宿主死亡率和终身传播潜力的影响-寄生虫健身的关键组成部分-使用啮齿动物疟疾模型，疟原虫chabaudi chabaudi。中和白细胞介素[IL]-10，一种重要的炎症调节因子，使我们能够通过实验增加8种寄生虫克隆的免疫病理学毒性比例。体内阻断IL-10受体（IL-10 R）与中和抗体导致较短的死亡时间，这是独立的寄生虫密度，特别是标记为正常无毒克隆。这表明IL-10诱导可能为P. c. chabaudi。尽管增加投资的传播阶段的寄生虫观察到一些克隆在响应IL-10 R封锁，实验增强免疫病理学引起了一个统一的健身成本，所有寄生虫克隆减少终身传播的潜力。这是第一个实验研究表明，感染诱导的免疫病理学和寄生虫遗传变异可能共同具有塑造毒力进化的潜力。与最近的理论雅阁，数据显示某些形式的免疫病理学可能选择使宿主不那么生病的寄生虫。
Explaining parasite virulence (harm to the host) represents a major challenge for evolutionary and biomedical scientists alike. Most theoretical models of virulence evolution assume that virulence arises as a direct consequence of host exploitation, the process whereby parasites convert host resources into transmission opportunities. However, infection-induced disease can be immune-mediated (immunopathology). Little is known about how immunopathology affects parasite fitness, or how it will affect the evolution of parasite virulence. Here we studied the effects of immunopathology on infection-induced host mortality rate and lifetime transmission potential – key components of parasite fitness – using the rodent malaria model, Plasmodium chabaudi chabaudi. Neutralizing interleukin [IL]-10, an important regulator of inflammation, allowed us to experimentally increase the proportion of virulence due to immunopathology for eight parasite clones. In vivo blockade of the IL-10 receptor (IL-10R) with a neutralizing antibody resulted in a shorter time to death that was independent of parasite density and was particularly marked for normally avirulent clones. This suggests that IL-10 induction may provide a pathway to avirulence for P. c. chabaudi. Despite the increased investment in transmission-stage parasites observed for some clones in response to IL-10R blockade, experimental enhancement of immunopathology incurred a uniform fitness cost to all parasite clones by reducing lifetime transmission potential. This is the first experimental study to demonstrate that infection-induced immunopathology and parasite genetic variability may together have the potential to shape virulence evolution. In accord with recent theory, the data show that some forms of immunopathology may select for parasites that make hosts less sick.
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影响因子：
3.7
作者：
Best, SM;Kerr, PJ
通讯作者：
Kerr, PJ
影响因子：
2.4
作者：
ANDERSON, RM;MAY, RM
通讯作者：
MAY, RM
DOI：
10.1098/rspb.2007.0809
发表时间：
2007-11-07
影响因子：
4.7
作者：
Day, Troy;Graham, Andrea L.;Read, Andrew F.
通讯作者：
Read, Andrew F.
影响因子：
4.4
作者：
Antonelli, LRV;Dutra, WO;Gollob, KJ
通讯作者：
Gollob, KJ
影响因子：
4
作者：
Buckling, AGJ;Read, AF
通讯作者：
Read, AF