Impairment of innate immune responses of airway epithelium by infection with bovine viral diarrhea virus
Impairment of innate immune responses of airway epithelium by infection with bovine viral diarrhea virus
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DOI：
10.1016/j.vetimm.2007.01.007
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发表时间：
2007-04-15
影响因子：
1.8
通讯作者：
Caswell, J. L.
中科院分区：
文献类型：
--
作者：
Al-Haddawi, A.;Mitchell, G. B.;Caswell, J. L.
牛病毒性腹泻病毒（BVDV）感染是饲养场牛发生运输热肺炎的重要风险因素，感染但不引起气道上皮细胞损伤的形态学证据。我们假设BVDV通过损害气道上皮细胞的先天性免疫应答而易患细菌性肺炎。用BVDV感染原代培养的牛气管上皮细胞48 μ l，然后用LPS刺激16 h。采用定量RT-PCR法检测气管抗菌肽（TAP）和舌抗菌肽（TFP）mRNA的表达，ELISA法检测培养上清中乳铁蛋白的含量。BVDV感染对TAP和TAPmRNA的组成型表达或培养上清液中的乳铁蛋白浓度没有可检测的影响。LPS处理引起培养物上清液中TAP mRNA表达和乳铁蛋白浓度显著增加（p < 0.01），并且这些效应被预先用2型ncp-BVDV分离株感染气管上皮细胞显著消除（p < 0.02，p < 0.01）。相反，I型ncp-BVDV分离株感染对TAP mRNA表达或乳铁蛋白分泌无影响。LPS处理诱导了BVDV mRNA表达的显著上调（p < 0.001），而先前感染BVDV对其无显著影响。这些数据表明，2型BVDV分离株感染可抑制LPS诱导的TAP mRNA表达上调和气管上皮细胞乳铁蛋白分泌，提示该病毒可消除牛的呼吸道先天免疫应答并易患细菌性肺炎的新机制。(c)2007 Elsevier B. V.保留所有权利。
Bovine viral diarrhea virus (BVDV) infection is an important risk factor for development of shipping fever pneumonia in feedlot cattle, and infects but does not cause morphologic evidence of damage to airway epithelial cells. We hypothesized that BVDV predisposes to bacterial pneumonia by impairing innate immune responses in airway epithelial cells. Primary cultures of bovine tracheal epithelial cells were infected with BVDV for 48 It, then stimulated with LPS for 16 h. Expression of tracheal antimicrobial peptide (TAP) and lingual antimicrobial peptide (LAP) mRNA was measured by quantitative RT-PCR, and lactoferrin concentrations were measured in culture supernatant by ELISA. BVDV infection had no detectable effect on the constitutive expression of TAP and LAP mRNA or lactoferrin concentration in culture supernatant. LPS treatment provoked a significant increase in TAP mRNA expression and lactoferrin concentration in the culture supernatant (p < 0.01), and these effects were significantly (p < 0.02, p < 0.01) abrogated by prior infection of the tracheal epithelial cells with the type 2 ncp-BVDV isolate. In contrast, infection with the type I ncp-BVDV isolate had no effect on TAP mRNA expression or lactoferrin secretion. LPS treatment induced a significant (p < 0.001) upregulation of LAP mRNA expression, which was not significantly affected by prior infection with BVDV. These data indicate that infection with a type 2 BVDV isolate inhibits the LPS-induced upregulation of TAP mRNA expression and lactoferrin secretion by tracheal epithelial cells, suggesting a novel mechanism by which this virus abrogates respiratory innate immune responses and predisposes to bacterial pneumonia in cattle. (c) 2007 Elsevier B.V. All rights reserved.