Characterization of NLRP12 during the in vivo host immune response to Klebsiella pneumoniae and Mycobacterium tuberculosis.
Characterization of NLRP12 during the in vivo host immune response to Klebsiella pneumoniae and Mycobacterium tuberculosis.
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DOI：
10.1371/journal.pone.0060842
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Ting JP
中科院分区：
文献类型：
--
作者：
Allen IC;McElvania-TeKippe E;Wilson JE;Lich JD;Arthur JC;Sullivan JT;Braunstein M;Ting JP
大多数核苷酸结合域富含亮氨酸重复序列（NLR）家族成员的功能尚未得到表征。在所描述的NLR中，大多数被认为是促炎性的并促进IL-1β的产生。然而，基于其减弱NF-κB信号传导的能力，已经鉴定了一个新定义的NLR亚组，其作为炎症的负调节剂发挥作用。NLRP 12（Monarch-1）是该亚组的原型成员，其在生化测定以及结肠炎和结肠癌模型中负调节经典和非经典NF-κB信号传导。NLRP 12在传染病中的作用尚未得到广泛研究。在这里，我们描述了Nlrp 12 −/−小鼠在气道暴露于LPS、肺炎克雷伯菌和结核分枝杆菌后的先天免疫反应。响应E. coli LPS，Nlrp 12 −/−小鼠显示IL-1β略有下降，IL-6产生增加，但这些水平无统计学意义。在K.在Nlrp 12 −/−小鼠中，我们观察到细胞因子水平的细微差异以及单核细胞和淋巴细胞数量的显著减少。然而，这些发现的生理相关性尚不清楚，因为在Nlrp 12 −/−小鼠中未观察到肺部疾病发展的明显差异。同样，Nlrp 12 −/−小鼠表现出与M.肺结核感染。总之，这些数据表明，NLRP 12对体内宿主对LPS刺激、肺炎克雷伯氏菌感染或结核分枝杆菌的先天免疫应答没有显著贡献。
The majority of nucleotide binding domain leucine rich repeats-containing (NLR) family members has yet to be functionally characterized. Of the described NLRs, most are considered to be proinflammatory and facilitate IL-1β production. However, a newly defined sub-group of NLRs that function as negative regulators of inflammation have been identified based on their abilities to attenuate NF-κB signaling. NLRP12 (Monarch-1) is a prototypical member of this sub-group that negatively regulates both canonical and noncanonical NF-κB signaling in biochemical assays and in colitis and colon cancer models. The role of NLRP12 in infectious diseases has not been extensively studied. Here, we characterized the innate immune response of Nlrp12−/− mice following airway exposure to LPS, Klebsiella pneumoniae and Mycobacterium tuberculosis. In response to E. coli LPS, Nlrp12−/− mice showed a slight decrease in IL-1β and increase in IL-6 production, but these levels were not statistically significant. During K. pneumoniae infection, we observed subtle differences in cytokine levels and significantly reduced numbers of monocytes and lymphocytes in Nlrp12−/− mice. However, the physiological relevance of these findings is unclear as no overt differences in the development of lung disease were observed in the Nlrp12−/− mice. Likewise, Nlrp12−/− mice demonstrated pathologies similar to those observed in the wild type mice following M. tuberculosis infection. Together, these data suggest that NLRP12 does not significantly contribute to the in vivo host innate immune response to LPS stimulation, Klebsiella pneumonia infection or Mycobacterium tuberculosis.
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DOI：
10.4049/jimmunol.0903937
发表时间：
2010-05-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
He X;Mekasha S;Mavrogiorgos N;Fitzgerald KA;Lien E;Ingalls RR
通讯作者：
Ingalls RR
影响因子：
4.4
作者：
Benko, Szilvia;Magalhaes, Joao G.;Girardin, Stephen E.
通讯作者：
Girardin, Stephen E.
影响因子：
3.4
作者：
Mishra, Bibhuti B.;Moura-Alves, Pedro;Anes, Elsa
通讯作者：
Anes, Elsa
影响因子：
5.4
作者：
Dorhoi, Anca;Nouailles, Geraldine;Kaufmann, Stefan H. E.
通讯作者：
Kaufmann, Stefan H. E.
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.