Inflammatory responses to pneumovirus infection in IFN-αBR gene-deleted mice
Inflammatory responses to pneumovirus infection in IFN-αBR gene-deleted mice
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DOI：
10.4049/jimmunol.175.7.4735
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发表时间：
2005-10-01
影响因子：
4.4
通讯作者：
Rosenberg, HF
中科院分区：
文献类型：
--
作者：
Garvey, TL;Dyer, KD;Rosenberg, HF
小鼠肺炎病毒（PVM；副粘病毒科）是啮齿动物的一种天然病原体，它能重现人类严重呼吸道合胞病毒感染的重要临床特征。正如所预期的那样，与干扰素 -αβR基因缺失（IFN -αβR -/-）小鼠相比，PVM感染优先诱导野生型小鼠的干扰素抗病毒反应基因转录。然而，我们证明，与野生型相比，PVM感染导致IFN -αβR -/-小鼠肺组织中嗜酸性粒细胞趋化因子 -2（CCL24）、胸腺和活化调节趋化因子（CCL17）以及促炎核糖核酸酶小鼠嗜酸性粒细胞相关核糖核酸酶（mEar）11的表达增强，单核细胞趋化蛋白 -5、干扰素 -γ诱导蛋白 -10和Toll样受体 -3的表达降低。未观察到趋化因子巨噬细胞炎性蛋白 -1α或巨噬细胞炎性蛋白 -2或Th2细胞因子白细胞介素 -4或白细胞介素 -5的差异表达。促炎介质的差异表达与肺部病理的不同模式相关。在PVM感染的野生型小鼠中观察到的广泛的粒细胞浸润和肺泡内水肿，被局限于较大血管周围的斑片状、密集炎症病灶所取代。来自IFN -αβR -/-小鼠的支气管肺泡灌洗液中白细胞总数减少了7 - 8倍，嗜酸性粒细胞、单核细胞和CD4(+) T细胞的百分比增加，CD8(+) T细胞的百分比降低。尽管病毒滴度增加，但不同的病理表现与IFN -αβR -/-小鼠的生存期延长相关（在10.8 ± 0.6天有50%存活，而野生型在9.0 ± 0.3天；p < 0.02）。总体而言，我们的研究结果有助于识别在有或没有干扰素 -αβR介导的信号传导情况下差异表达的新转录本，进一步阐明体内干扰素与抗病毒炎症反应之间的相互作用。
Pneumonia virus of mice (PVM; family Paramyxoviridae) is a natural pathogen of rodents that reproduces important clinical features of severe respiratory syncytial virus infection in humans. As anticipated, PVM infection induces transcription of IFN antiviral response genes preferentially in wild-type over IFN-alpha beta R gene-deleted (IFN-alpha beta R-/-) mice. However, we demonstrate that PVM infection results in enhanced expression of eotaxin-2 (CCL24), thymus and activation-regulated chemokine (CCL17), and the proinflammatory RNase mouse eosinophil-associated RNase (mEar) 11, and decreased expression of monocyte chemotactic protein-5, IFN-gamma-inducible protein-10, and TLR-3 in lung tissue of IFN-alpha beta R-/- mice when compared with wild type. No differential expression of chemokines MIP-1 alpha or MIP-2 or Th2 cytokines IL-4 or IL-5 was observed. Differential expression of proinflammatory mediators was associated with distinct patterns of lung pathology. The widespread granulocytic infiltration and intra-alveolar edema observed in PVM-infected, wild-type mice are replaced with patchy, dense inflammatory foci localized to the periphery of the larger blood vessels. Bronchoalveolar lavage fluid from IFN-alpha beta R-/- mice yielded 7- to 8-fold fewer leukocytes overall, with increased percentages of eosinophils, monocytes, and CD4(+) T cells, and decreased percentage of CD8(+) T cells. Differential pathology is associated with prolonged survival of the IFN-alpha beta R-/- mice (50% survival at 10.8 +/- 0.6 days vs the wild type at 9.0 +/- 0.3 days; p < 0.02) despite increased virus titers. Overall, our findings serve to identify novel transcripts that are differentially expressed in the presence or absence of IFN-alpha beta R-mediated. signaling, further elucidating interactions between the IFN and antiviral inflammatory responses in vivo.