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免疫接种对疟原虫感染内竞争的影响。

The impact of immunization on competition within Plasmodium infections.

作者信息

Grech Katrina, Chan Brian H K, Anders Robin F, Read Andrew F

机构信息

Institutes of Evolutionary Biology & Immunology and Infection Research, School of Biological Sciences, Ashworth Laboratories, University of Edinburgh, Edinburgh EH9 3JT, Scotland, United Kingdom.

出版信息

Evolution. 2008 Sep;62(9):2359-71. doi: 10.1111/j.1558-5646.2008.00438.x. Epub 2008 Jun 6.

Abstract

Evolutionary theory argues that ecological interactions between pathogens within an infection can be a potent source of selection shaping traits such as virulence, drug resistance, and infectiousness. In humans, malaria infections are frequently genetically diverse, with mixed genotype infections the norm. A wide variety of evidence shows that crowding occurs within infections, with the population densities of individual genotypes suppressed by the presence of others. Public health interventions are expected to impact on levels of immunity experienced by pathogens, indirectly by reducing the rate of acquisition of natural immunity by reducing the force of infection, and directly in the case of vaccination programs. Here we ask how enhanced host immunity affects competitive interactions between malaria parasites within hosts and thus the strength of in-host selection on traits such as virulence. We used a model malaria system, Plasmodium chabaudi in laboratory mice, where it has been previously shown that less virulent parasites are competitively suppressed by more virulent strains, generating within-host selection for increased virulence. We found that immunization with either a recombinant antigen or with live parasites suppressed parasite densities, but that there was no evidence that immunization relieved or exacerbated competitive suppression, or affected the relative frequency of clones within infections. There is thus no reason to think that immunization strengthens or alleviates the potentially very potent selection on parasite traits arising from interactions between pathogen genotypes within infections.

摘要

进化理论认为,感染体内病原体之间的生态相互作用可能是塑造毒力、耐药性和传染性等性状的强大选择来源。在人类中,疟疾感染通常在基因上具有多样性,混合基因型感染很常见。大量证据表明,感染体内会出现拥挤现象,其他基因型的存在会抑制单个基因型的种群密度。公共卫生干预措施预计会对病原体所经历的免疫水平产生影响,间接影响是通过降低感染强度来减少自然免疫的获得率,而在疫苗接种计划中则是直接产生影响。在此,我们探讨增强的宿主免疫力如何影响宿主体内疟原虫之间的竞争相互作用,进而影响对毒力等性状的宿主体内选择强度。我们使用了一个疟疾模型系统,即实验室小鼠体内的查巴迪疟原虫,此前已表明,毒力较弱的寄生虫会被毒力较强的菌株竞争性抑制,从而在宿主体内产生对增加毒力的选择。我们发现,用重组抗原或活寄生虫进行免疫会抑制寄生虫密度,但没有证据表明免疫会减轻或加剧竞争性抑制,也不会影响感染内克隆的相对频率。因此,没有理由认为免疫会加强或减轻因感染体内病原体基因型之间的相互作用而对寄生虫性状产生的潜在非常强大的选择。

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