Functional Disorder of Primary Immunity Responding to Respiratory Syncytial Virus Infection in Offspring Mice Exposed to a Flame Retardant, Decabrominated Diphenyl Ether, Perinatally
Functional Disorder of Primary Immunity Responding to Respiratory Syncytial Virus Infection in Offspring Mice Exposed to a Flame Retardant, Decabrominated Diphenyl Ether, Perinatally
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DOI：
10.1002/jmv.21770
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发表时间：
2010-06-01
影响因子：
12.7
通讯作者：
Kurokawa, Masahiko
中科院分区：
文献类型：
--
作者：
Watanabe, Wataru;Shimizu, Tomomi;Kurokawa, Masahiko
围产期暴露于一种代表性的阻燃剂十溴二苯醚（DBDE）之前已被证明会增加呼吸道合胞病毒（RSV）感染后代在感染后第5天肺部的病毒滴度，导致肺炎恶化。在这项研究中，甚至在感染后第1天就证实了肺部病毒滴度的显著增加，并检查了对RSV感染的初级免疫反应的影响，以评估DBDE对发育免疫毒性的作用模式。感染后第1天，RSV感染后代经DBDE永久暴露后制备的支气管肺泡灌洗液中TNF-α和IL-6的分泌均显著降低，但IL-1 β升高。然而，在离体脂多糖刺激试验中，支气管肺泡灌洗液细胞中TNF-α的产生率，其主要是对RSV感染应答的初级免疫细胞，从围产期暴露于DBDE的后代小鼠制备的血清中的总胆固醇含量不低于对照组。暴露于十溴二苯醚后，初级免疫细胞保持了正常的细胞因子产生能力。肺组织中先天模式识别受体（Toll样受体3和4、黑色素瘤分化相关基因5和视黄酸诱导基因I）的基因表达不受暴露于十溴二苯醚的影响。由于已知RSV感染小鼠的肺中TNF-α、IL-6和IL-1 β水平升高，因此由于围产期DBDE暴露导致的这些不规则产生表明对RSV感染的初级免疫应答紊乱。因此，围产期接触十溴二苯醚可能会导致对RSV感染作出反应的初级免疫功能紊乱。J. Med. Virol. 82：1075- 1082，2010。(C)2010 Wiley-Liss，Inc
Perinatal exposure to a representative flame retardant, decabrominated diphenyl ether (DBDE), was shown previously to increase viral titers in the lungs of respiratory syncytial virus (RSV)infected offspring on day 5 post-infection, resulting in exacerbation of pneumonia. In this study, the significant increase of pulmonary viral titers was confirmed even on day 1 post-infection and the effect on the primary immune response to RSV infection were examined to assess a mode of DBDE action on developmental immunotoxicity. On day 1 after infection, the secretion of both TNF-alpha and IL-6 decreased significantly in the bronchoalveolar lavage fluid prepared from RSV-infected offspring exposed to DBDE permatally, but IL-1 beta increased However, in ex vivo lippolysaccharide stimulation test, the productivity of TNF-alpha in the bronchoalveolar lavage cells, which are mainly primary immune cells responding to RSV infection, prepared from offspring mice exposed to DBDE perinatally was not lower than that in the control. The primary immune cells retained normally the ability of cytokine production after the DBDE exposure Gene expressions of innate pattern recognition receptors (Toll-like receptor 3 and 4, melanoma differentiation-associated gene-5, and retinoic acid-inducible gene I) in lung tissues were not affected by DBDE exposure. Because the levels of TNF-a, IL-6, and IL-1 beta are known to be elevated in the lungs of RSV-infected mice, these irregular productions due to perinatal DBDE exposure indicate a disorder of the primary immune response to RSV infection. Thus, perinatal exposure to DBDE was suggested to cause a functional disorder of primary immunity responding to RSV infection. J. Med. Virol. 82:1075-1082,2010. (C) 2010 Wiley-Liss, Inc