Cressler Clayton E, Adelman James S
School of Biological Sciences, The University of Nebraska, Lincoln, Lincoln, NE 68588, USA.
Department of Biological Sciences, The University of Memphis, Memphis, TN 39152, USA.
Integr Comp Biol. 2024 Sep 27;64(3):841-852. doi: 10.1093/icb/icae105.
Immunopathology, or the harm caused to an organism's own tissues during the activation of its immune system, carries substantial costs. Moreover, avoiding this self-harm may be an important mechanism underlying tolerance of infection, helping to reducing fitness costs without necessarily clearing parasites. Despite the apparent benefits of minimizing immunopathology, such damage persists across a range of host species. Prior work has explored a trade-off with resistance during a single infection as a potential driver of this persistence, with some collateral damage being unavoidable when killing parasites. Here, we present an additional trade-off that could favor the continued presence of immunopathology: robust immune responses during initial infection (e.g., innate immunity in vertebrates) can induce stronger memory (adaptive immunity), offering protection from future infections. We explore this possibility in an adaptive dynamics framework, using theoretical models parameterized from an ecologically relevant host-parasite system, house finches (Haemorhous mexicanus) infected with the bacterial pathogen, Mycoplasma gallisepticum. We find that some degree of immunopathology is often favored when immunopathology during first infection either reduces susceptibility to or enhances recovery from second infection. Further, interactions among factors like transmission rate, recovery rate, background mortality, and pathogen virulence also shape these evolutionary dynamics. Most notably, the evolutionary stability of investment in immunopathology is highly dependent upon the mechanism by which hosts achieve secondary protection (susceptibility vs. recovery), with the potential for abrupt evolutionary shifts between high and low investment under certain conditions. These results highlight the potential for immune memory to play an important role in the evolutionary persistence of immunopathology and the need for future empirical research to reveal the links between immunopathology during initial infections and longer-term immune protection.
免疫病理学，即生物体免疫系统激活过程中对自身组织造成的损害，会带来巨大代价。此外，避免这种自身伤害可能是感染耐受性的一个重要机制，有助于降低健康成本，而不一定需要清除寄生虫。尽管将免疫病理学降至最低有明显益处，但这种损害在一系列宿主物种中依然存在。先前的研究探讨了在单一感染过程中与抵抗力的权衡，认为这是这种持续性的潜在驱动因素，即杀死寄生虫时一些附带损害不可避免。在此，我们提出另一种可能有利于免疫病理学持续存在的权衡：初次感染期间强烈的免疫反应（如脊椎动物的先天免疫）可诱导更强的记忆（适应性免疫），为未来感染提供保护。我们在一个适应性动态框架中探讨这种可能性，使用从一个具有生态相关性的宿主 - 寄生虫系统（感染细菌病原体鸡败血支原体的家朱雀）参数化的理论模型。我们发现，当初次感染期间的免疫病理学降低对二次感染的易感性或增强从二次感染中恢复的能力时，某种程度的免疫病理学往往更受青睐。此外，传播率、恢复率、背景死亡率和病原体毒力等因素之间的相互作用也塑造了这些进化动态。最值得注意的是，对免疫病理学的投资的进化稳定性高度依赖于宿主实现二次保护的机制（易感性与恢复），在某些条件下，投资水平可能会在高和低之间发生突然的进化转变。这些结果凸显了免疫记忆在免疫病理学进化持续性中发挥重要作用的潜力，以及未来实证研究揭示初次感染期间的免疫病理学与长期免疫保护之间联系的必要性。
