The interaction of pollutants and pathogens may result in altered and often enhanced effects of the chemical, the biotic stressor or both. These interaction effects cannot be reliably predicted from the toxicity of the chemical or the virulence of the pathogen alone. While standardized detection methods for immunotoxic effects of chemicals exist with regard to human health, employing host-resistance assays with vertebrates, such standardized test systems are completely lacking for invertebrate species and no guidance is available on how immunotoxic effects of a chemical in invertebrates could be definitively identified. In the present study, we investigated the impact of the immunosuppressive pharmaceutical cyclosporine A (CsA) on the invertebrate host-pathogen system Daphnia magna – Pasteuria ramosa. CsA is a calcineurin-inhibitor in vertebrates and also known to have antibiotic as well as antifungal properties. Juvenile D. magna were exposed to CsA for 21 days with or without additional pathogen challenge during the first 72 h of exposure. Long-term survival of the host D. magna was synergistically impacted by co-exposure to the chemical and the pathogen, expressed e.g. in significantly enhanced hazard ratios. Additionally, enhanced virulence of the pathogen upon chemical co-exposure was expressed in an increased proportion of infected hosts and an increased speed of Pasteuria-induced host sterilization. In contrast, effects on reproduction were additive in Pasteuria-challenged, but finally non-infected D. magna. The enhancing effects of CsA occurred at and below 3 μg/L, which was in the absence of the pathogen the lowest concentration significantly impacting the standard toxicity endpoint ‘reproduction’ in D. magna. Hence, the present study provides evidence that a pharmaceutical intended to suppress the human immune system can also suppress disease resistance of an aquatic invertebrate organism at otherwise non-toxic concentrations. Plausible ways of direct interactions of CsA with the host’s immune system are discussed, e.g. interference with phagocytosis or Toll-like receptors. Experimental verification of such a direct interference would be warranted to support the strong evidence for immunotoxic activity of CsA in invertebrates. While it remains open whether CsA concentrations in the environment are high enough to trigger adverse effects in environmental organisms, our findings highlight the need to consider immunotoxicity in an environmental risk assessment, and to develop suitable standardized methods for this purpose.

污染物和病原体的相互作用可能会导致化学物质，生物应激物或两者的作用发生改变，并且通常会增强作用。仅从化学毒性或病原体的毒力无法可靠地预测这些相互作用的影响。尽管存在针对人类健康的化学药品免疫毒性作用的标准化检测方法，但对脊椎动物进行宿主抗性测定，却完全缺乏针对无脊椎动物物种的此类标准化测试系统，并且尚无关于如何化学药品对无脊椎动物免疫毒性的指南。明确确定。在本研究中，我们调查了免疫抑制药物环孢菌素A（CsA）对无脊椎动物宿主-病原体水蚤（Daphnia magna）的影响–巴氏巴斯德氏菌。CsA是脊椎动物中的钙调神经磷酸酶抑制剂，并且还具有抗生素和抗真菌特性。少年D.蚤曝光的第一个72小时内暴露于环孢素21天用或不用附加的病原体攻击。共同暴露于化学物质和病原体会协同影响寄主D. magna的长期存活，例如以显着提高的危险比表示。另外，在化学共同暴露下，病原体的毒力增强表现为感染宿主比例的增加和巴斯德氏菌诱导的宿主绝育速度的提高。相比之下，巴斯德氏菌对生殖的影响是加性的-受到挑战，但最终未感染D. magna。CsA的增强作用在3μg/ L或以下时发生，这是在没有病原体的情况下，最低浓度会显着影响D. magna的标准毒性终点“繁殖”。因此，本研究提供了证据，旨在抑制人类免疫系统的药物也可以在其他无毒浓度下抑制水生无脊椎动物的抗病性。讨论了CsA与宿主免疫系统直接相互作用的可能方式，例如干扰吞噬作用或Toll样受体。这种直接干扰的实验验证将有必要为无脊椎动物CsA的免疫毒性活性提供有力证据。尽管环境中CsA的浓度是否足够高以引发对环境生物的不利影响尚不明确，但我们的发现强调了在环境风险评估中需要考虑免疫毒性，并为此目的开发合适的标准化方法。