Protection Generated by Prior Exposure to Pathogens Depends on both Priming and Challenge Dose
Protection Generated by Prior Exposure to Pathogens Depends on both Priming and Challenge Dose
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先前暴露于病原体所产生的保护取决于引发剂量和激发剂量
DOI：
10.1128/iai.00537-21
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发表时间：
2022
影响因子：
3.1
通讯作者：
Hawley, Dana M.
中科院分区：
文献类型：
--
作者：
Weitzman, Chava L.;Ceja, Guadalupe;Leon, Ariel E.;Hawley, Dana M.
自由生活的宿主遇到各种频率和浓度的病原体，包括基本上无临床的低剂量，从而形成不同的暴露史和再感染可能性。虽然一些研究表明，较高的引发剂量导致更强的免疫保护，防止再感染，它仍然是未知的再感染的挑战剂量和引发剂量如何相互作用，以确定再感染的可能性和严重程度。我们操纵引发和挑战剂量的鸡毒支原体，导致支原体结膜炎，圈养家雀（墨西哥血喉），以评估再感染的概率和严重程度。我们发现了一个显着的相互作用之间的启动和挑战剂量的再感染概率，再感染的可能性高，但不是低的挑战剂量在较高的启动剂量呈指数下降。虽然这种相互作用可能是由低剂量与高剂量攻毒的平均感染概率较低驱动的，但即使是最高的引发剂量也只能提供可忽略不计的保护，防止低剂量攻毒的再感染。同样，再次感染期间的病原体负荷显着减少，增加引发剂量，只有在高剂量而不是低剂量再次感染的鸟类。我们假设这些相互作用在一定程度上是由于不同剂量的宿主免疫反应的根本差异引起的，单次低剂量只能微弱地触发宿主免疫反应。重要的是，我们的研究结果还表明，再感染可以发生在各种暴露剂量和不同程度的常设免疫系统中。总的来说，我们的研究强调了考虑初始和后续暴露剂量的重要性，其中重复暴露于病原体在自然界中很常见。
Free-living hosts encounter pathogens at a wide range of frequencies and concentrations, including low doses that are largely aclinical, creating a varied landscape of exposure history and reinfection likelihood. While several studies show that higher priming doses result in stronger immunological protection against reinfection, it remains unknown how the reinfection challenge dose and priming dose interact to determine the likelihood and severity of reinfection. We manipulated both priming and challenge doses of Mycoplasma gallisepticum, which causes mycoplasmal conjunctivitis, in captive house finches (Haemorhous mexicanus), to assess reinfection probability and severity. We found a significant interaction between priming and challenge doses on reinfection probability, with the likelihood of reinfection by a high but not a low challenge dose decreasing exponentially at higher priming doses. While this interaction was likely driven by lower average infection probabilities for low-dose versus high-dose challenges, even the highest priming dose provided only negligible protection against reinfection from low-dose challenges. Similarly, pathogen loads during reinfection were significantly reduced with increasing priming doses only for birds reinfected at high but not low doses. We hypothesize that these interactions arise to some degree from fundamental differences in host immune responses across doses, with single low doses only weakly triggering host immune responses. Importantly, our results also demonstrate that reinfections can occur from a variety of exposure doses and across diverse degrees of standing immunity in this system. Overall, our study highlights the importance of considering both initial and subsequent exposure doses where repeated exposure to a pathogen is common in nature.
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影响因子：
2.7
作者：
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通讯作者：
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作者：
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