Chlamydia pneumoniae harness host NLRP3 inflammasome-mediated caspase-1 activation for optimal intracellular growth in murine macrophages
Chlamydia pneumoniae harness host NLRP3 inflammasome-mediated caspase-1 activation for optimal intracellular growth in murine macrophages
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DOI：
10.1016/j.bbrc.2014.08.128
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发表时间：
2014-09-26
影响因子：
3.1
通讯作者：
Hiromatsu, Kenji
中科院分区：
文献类型：
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作者：
Itoh, Ryota;Murakami, Issaku;Hiromatsu, Kenji
肺炎衣原体是一种专性细胞内病原体，在空泡内复制并获得宿主细胞营养。我们证明了C.肺炎链球菌利用宿主先天免疫信号传导NLRP 3/ASC/半胱天冬酶-1炎性体进行细胞内生长。骨髓源性巨噬细胞（BmM）在感染C.肺炎，这取决于NLRP 3炎性体激活。C.在来自Nlrp 3（-/-）、Asc（-/-）和Casp 1（-/-）小鼠的BclB中，肺炎链球菌感染严重受损，但在野生型或Nlrc 4（-/-）小鼠中没有。此外，有缺陷的NLRP 3炎性体组分导致脂滴在感染的双歧杆菌内积聚，表明在不存在NLRP 3炎性体活化的情况下脂质的摄取和/或利用受到干扰。这些结果提示C.肺炎克雷伯氏菌已经进化为利用宿主先天免疫应答和NLRP 3炎性体激活，以获得细胞内生长所必需的必需营养素。C. pneumoniae可能为C.肺炎增加动脉粥样硬化和代谢综合征的风险。(C)2014爱思唯尔公司All rights reserved.
Chlamydia pneumoniae is an obligate intracellular pathogen that replicates within a vacuole and acquires host cell nutrients. We show that C. pneumoniae utilizes host innate immune signaling NLRP3/ASC/caspase-1 inflammasome for intracellular growth. Bone marrow-derived macrophages (BMMs) secreted mature interleukin-1 beta upon infection with C. pneumoniae depending on the NLRP3 inflammasome activation. Intracellular growth of C. pneumoniae was severely impaired in BMMs from Nlrp3(-/-), Asc(-/-) and Casp1(-/-) mice but not wild type or Nlrc4(-/-) mice. Furthermore defective NLRP3 inflammasome components led to accumulation of lipid droplets inside the infected BMMs, suggesting that uptake and/or utilization of lipids is disturbed in the absence of NLRP3 inflammasome activation. These results suggest C. pneumoniae has evolved to harness both host innate immune response and NLRP3 inflammasome activation, for the acquisition of essential nutrients necessary for intracellular growth. This unique property of C. pneumoniae may shed a new light on how C. pneumoniae increase the risk of atherosclerosis and metabolic syndrome. (C) 2014 Elsevier Inc. All rights reserved.