Macrophage activation state determines the response to rhinovirus infection in a mouse model of allergic asthma.
Macrophage activation state determines the response to rhinovirus infection in a mouse model of allergic asthma.
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DOI：
10.1186/1465-9921-15-63
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发表时间：
2014-06-07
影响因子：
5.8
通讯作者：
Hershenson MB
中科院分区：
文献类型：
--
作者：
Hong JY;Chung Y;Steenrod J;Chen Q;Lei J;Comstock AT;Goldsmith AM;Bentley JK;Sajjan US;Hershenson MB
病毒引起哮喘恶化的机制尚不清楚。以前，我们发现，在卵清蛋白（OVA）致敏和过敏性气道炎症的小鼠，鼻病毒（RV）感染增加2型细胞因子的生产从交替激活（M2）的气道巨噬细胞，增强嗜酸性粒细胞炎症和气道高反应性。在这篇论文中，我们检验了IL-4信号传导决定巨噬细胞活化状态和RV诱导的过敏性气道疾病小鼠加重模式的假设。将8周龄的野生型或IL-4受体敲除（IL-4 R KO）小鼠致敏并用OVA攻击，并用RV 1B或假HeLa细胞裂解物接种。与同时具有嗜酸性粒细胞和嗜酸性粒细胞气道炎症的OVA处理的野生型小鼠相比，OVA处理的IL-4 R KO小鼠显示出增加的嗜酸性粒细胞炎症，气道中几乎没有嗜酸性粒细胞。与野生型小鼠一样，IL-4 R KO小鼠表现出OVA诱导的气道高反应性，RV进一步加剧了这种高反应性。肺细胞因子从2型为主的应答转变为1型应答，包括产生IL-12 p40和TNF-α。IL-17 A也增加。OVA处理的IL-4 R KO小鼠的RV感染进一步增加了嗜酸性炎症。支气管肺泡巨噬细胞显示M1极化模式，离体RV感染增加巨噬细胞产生TNF-α、IFN-γ和IL-12 p40。最后，来自OVA处理的IL-4 R KO小鼠的肺细胞显示出减少的CD 206 + CD 301 + M2巨噬细胞、减少的IL-13和增加的TNF-α和IL-17 A由F4/80+、CD 11b+巨噬细胞产生。经OVA处理的IL-4 R KO小鼠显示构成过敏性、1型尼古丁驱动的嗜肺性哮喘模型的嗜肺性气道炎症。在缺乏IL-4/IL-13信号传导的情况下，OVA处理的小鼠的RV感染增加了常规活化的巨噬细胞的1型细胞因子和IL-17 A的产生，增加了嗜酸性粒细胞而不是嗜酸性粒细胞炎症。在患有过敏性气道炎症的小鼠中，IL-4 R信号传导决定巨噬细胞活化状态和对随后RV感染的反应。
The mechanisms by which viruses cause asthma exacerbations are not precisely known. Previously, we showed that, in ovalbumin (OVA)-sensitized and -challenged mice with allergic airway inflammation, rhinovirus (RV) infection increases type 2 cytokine production from alternatively-activated (M2) airway macrophages, enhancing eosinophilic inflammation and airways hyperresponsiveness. In this paper, we tested the hypothesis that IL-4 signaling determines the state of macrophage activation and pattern of RV-induced exacerbation in mice with allergic airways disease. Eight week-old wild type or IL-4 receptor knockout (IL-4R KO) mice were sensitized and challenged with OVA and inoculated with RV1B or sham HeLa cell lysate. In contrast to OVA-treated wild-type mice with both neutrophilic and eosinophilic airway inflammation, OVA-treated IL-4R KO mice showed increased neutrophilic inflammation with few eosinophils in the airways. Like wild-type mice, IL-4R KO mice showed OVA-induced airway hyperreactivity which was further exacerbated by RV. There was a shift in lung cytokines from a type 2-predominant response to a type 1 response, including production of IL-12p40 and TNF-α. IL-17A was also increased. RV infection of OVA-treated IL-4R KO mice further increased neutrophilic inflammation. Bronchoalveolar macrophages showed an M1 polarization pattern and ex vivo RV infection increased macrophage production of TNF-α, IFN-γ and IL-12p40. Finally, lung cells from OVA-treated IL-4R KO mice showed reduced CD206+ CD301+ M2 macrophages, decreased IL-13 and increased TNF-α and IL-17A production by F4/80+, CD11b+ macrophages. OVA-treated IL-4R KO mice show neutrophilic airway inflammation constituting a model of allergic, type 1 cytokine-driven neutrophilic asthma. In the absence of IL-4/IL-13 signaling, RV infection of OVA-treated mice increased type 1 cytokine and IL-17A production from conventionally-activated macrophages, augmenting neutrophilic rather than eosinophilic inflammation. In mice with allergic airways inflammation, IL-4R signaling determines macrophage activation state and the response to subsequent RV infection.
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DOI：
10.1164/ajrccm/136.1.36
发表时间：
1987-07-01
期刊：
AMERICAN REVIEW OF RESPIRATORY DISEASE
影响因子：
--
作者：
FABBRI, LM;BOSCHETTO, P;MAPP, CE
通讯作者：
MAPP, CE
DOI：
10.4049/jimmunol.1200385
发表时间：
2012-06-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Griffin GK;Newton G;Tarrio ML;Bu DX;Maganto-Garcia E;Azcutia V;Alcaide P;Grabie N;Luscinskas FW;Croce KJ;Lichtman AH
通讯作者：
Lichtman AH
DOI：
10.1165/rcmb.2004-0417oc
发表时间：
2006-02-01
影响因子：
6.4
作者：
Chen, Y;Hamati, E;Wu, R
通讯作者：
Wu, R
影响因子：
3
作者：
Ford AQ;Dasgupta P;Mikhailenko I;Smith EM;Noben-Trauth N;Keegan AD
通讯作者：
Keegan AD
DOI：
10.1164/ajrccm.160.5.9806170
发表时间：
1999-11-01
影响因子：
24.7
作者：
Jatakanon, A;Uasuf, C;Barnes, PJ
通讯作者：
Barnes, PJ