Curtis Lawrence R, Bravo Claudia F, Bayne Christopher J, Tilton Fred, Arkoosh Mary R, Lambertini Elisabetta, Loge Frank J, Collier Tracy K, Meador James P, Tilton Susan C
Department of Environmental and Molecular Toxicology, Oregon State University, ALS 1007, Corvallis, OR 97331, USA.
Department of Integrative and Comparative Biology, Oregon State University, Cordley 3029, Corvallis, OR 97331, USA.
Ecotoxicol Environ Saf. 2017 Aug;142:157-163. doi: 10.1016/j.ecoenv.2017.03.044. Epub 2017 Apr 11.
We previously observed that exposure to a complex mixture of high molecular weight polycyclic aromatic hydrocarbons (PAHs) increased sensitivity of rainbow trout (Oncorhynchus mykiss) to subsequent challenge with Aeromonas salmonicida, the causative agent of furunculosis. In this study, we evaluate potential mechanisms associated with disease susceptibility from combined environmental factors of dietary PAH exposure and pathogen challenge. Rainbow trout were fed a mixture of ten high molecular weight PAHs at an environmentally relevant concentration (7.82μg PAH mixture/g fish/day) or control diet for 50 days. After 50 days of PAH exposure, fish were challenged with either Aeromonas salmonicida at a lethal concentration 30 (LC) or growth media without the pathogen (mock challenge). Head kidneys were collected 2, 4, 10 and 20 days after challenge and gene expression (q<0.05) was evaluated among treatments. In animals fed the PAH contaminated diet, we observed down-regulation of expression for innate immune system genes in pathways (p<0.05) for the terminal steps of the complement cascade (complement component C6) and other bacteriolytic processes (lysozyme type II) potentially underlying increased disease susceptibility after pathogen challenge. Increased expression of genes associated with hemorrhage/tissue remodeling/inflammation pathways (p<0.05) was likely related to more severe head kidney damage due to infection in PAH-fed compared to control-fed fish. This study is the first to evaluate transcriptional signatures associated with the impact of chronic exposure to an environmentally relevant mixture of PAHs in disease susceptibility and immunity.
我们之前观察到，暴露于高分子量多环芳烃（PAHs）的复杂混合物中会增加虹鳟（Oncorhynchus mykiss）对随后感染杀鲑气单胞菌（Aeromonas salmonicida）（疖疮病的病原体）的敏感性。在本研究中，我们评估了饮食中PAH暴露和病原体感染这两种环境因素共同作用下与疾病易感性相关的潜在机制。将虹鳟喂食含有环境相关浓度（7.82μg PAH混合物/克鱼/天）的十种高分子量PAHs的混合物或对照饲料，持续50天。在PAH暴露50天后，用致死浓度30（LC）的杀鲑气单胞菌或不含病原体的生长培养基（模拟感染）对鱼进行感染。在感染后2、4、10和20天收集头肾，并评估各处理组之间的基因表达（q<0.05）。在喂食受PAH污染饲料的动物中，我们观察到补体级联反应终末步骤（补体成分C6）和其他潜在的溶菌过程（II型溶菌酶）途径中的先天免疫系统基因表达下调（p<0.05），这可能是病原体感染后疾病易感性增加的潜在原因。与喂食对照饲料的鱼相比，喂食PAH饲料的鱼中与出血/组织重塑/炎症途径相关的基因表达增加（p<0.05），这可能与感染导致的更严重的头肾损伤有关。本研究首次评估了与长期暴露于环境相关PAH混合物对疾病易感性和免疫力影响相关的转录特征。
