Inflammation and fibrosis during Chlamydia pneumoniae infection is regulated by IL-1 and the NLRP3/ASC inflammasome.
Inflammation and fibrosis during Chlamydia pneumoniae infection is regulated by IL-1 and the NLRP3/ASC inflammasome.
复制标题
DOI：
10.4049/jimmunol.0903937
复制
发表时间：
2010-05-15
期刊：
影响因子：
--
通讯作者：
Ingalls RR
中科院分区：
文献类型：
--
作者：
He X;Mekasha S;Mavrogiorgos N;Fitzgerald KA;Lien E;Ingalls RR
肺炎衣原体是一种常见的呼吸道病原体与非典型肺炎，它已被认为是一个触发器或促进几种慢性炎症性疾病，如哮喘和动脉粥样硬化。IL-1 β（IL-1β）是一种由多种细胞释放的促炎细胞因子，是感染过程中重要的炎症介质。IL-1β的产生是一个严格控制的过程，包括多个水平的调节，通常需要两个不同的信号来激活和释放。在这项研究中，我们调查了C。pneumoniae）诱导IL-1β分泌。我们发现C.肺炎衣原体在其他测试的衣原体物种中是独特的，其能够在生产性感染期间有效诱导未致敏的骨髓来源的巨噬细胞分泌成熟IL-1β。TLR 2是诱导pro-IL-1β所必需的，而NLRP 3/ASC是半胱天冬酶-1活化和pro-IL-1β切割以产生成熟IL-1β所必需的。Caspase-1裂解是独立的内源性ATP释放，但需要钾流量，溶酶体酸化，和组织蛋白酶B释放。我们进一步研究了IL-1在宿主防御C.使用I型IL-1 R缺陷的小鼠进行肺炎诱导的肺炎。尽管IL-1 R −/−小鼠出现了炎症浸润，但浸润的中性粒细胞数量较低，而有证据表明浸润的成纤维细胞和间充质细胞增加，肺纤维化增加。结果表明，C.肺炎链球菌直接激活NLRP 3/ASC炎性体，导致生物活性IL-1β的释放，并且同时的IL-1信号传导是针对急性细菌性肺炎的最佳宿主防御所必需的。
Chlamydia pneumoniae is a common respiratory pathogen associated with atypical pneumonia, and it has been suggested as a trigger or promoter of several chronic inflammatory conditions, such as asthma and atherosclerosis. The β form of IL-1 (IL-1β) is a proinflammatory cytokine released by many cell types and is an important mediator of inflammation during infection. IL-1β production is a tightly controlled process that includes regulation at multiple levels and typically requires two distinct signals for activation and release. In this study, we investigated the ability of C. pneumoniae to induce IL-1β secretion. We found that C. pneumoniae was unique among the other Chlamydia species tested in its ability to potently induce secretion of mature IL-1β from unprimed bone marrow-derived macrophages during a productive infection. TLR2 was required for induction of pro–IL-1β, whereas the NLRP3/ASC was required for caspase-1 activation and pro–IL-1β cleavage to produce mature IL-1β. Caspase-1 cleavage was independent of endogenous ATP release, but required potassium flux, lysosomal acidification, and cathepsin B release. We further investigated the role of IL-1 in host defense against C. pneumoniae-induced pneumonia using mice deficient in the type I IL-1R. Although the IL-1R−/− mice developed an inflammatory infiltrate, the number of infiltrating neutrophils was lower, whereas there was evidence of increased infiltrating fibroblasts and mesenchymal cells and more lung fibrosis. We conclude that C. pneumoniae directly activates the NLRP3/ASC inflammasome, leading to the release of biologically active IL-1β, and that concurrent IL-1 signaling is required for optimal host defense against acute bacterial pneumonia.
登录
查看更多内容
DOI：
10.1152/ajplung.2000.279.6.l1184
发表时间：
2000-12-01
影响因子：
4.9
作者：
Geiser, T;Jarreau, PH;Matthay, MA
通讯作者：
Matthay, MA
影响因子：
3.5
作者：
Bailey, Leslie;Gylfe, Asa;Bergstrom, Sven
通讯作者：
Bergstrom, Sven
影响因子：
30.5
作者：
通讯作者：
--
影响因子：
32.4
作者：
Allen, Irving C.;Scull, Margaret A.;Moore, Chris B.;Holl, Eda K.;McElvania-TeKippe, Erin;Taxman, Debra J.;Guthrie, Elizabeth H.;Pickles, Raymond J.;Ting, Jenny P. -Y.
通讯作者：
Ting, Jenny P. -Y.
影响因子：
56.9
作者：
Dostert, Catherine;Petrilli, Virginie;Tschopp, Jurg
通讯作者：
Tschopp, Jurg