Role of the chemokine decoy receptor D6 in balancing inflammation, immune activation, and antimicrobial resistance in Mycobacterium tuberculosis infection.
Role of the chemokine decoy receptor D6 in balancing inflammation, immune activation, and antimicrobial resistance in Mycobacterium tuberculosis infection.
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DOI：
10.1084/jem.20070608
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发表时间：
2008-09-01
期刊：
影响因子：
--
通讯作者：
Mantovani A
中科院分区：
文献类型：
--
作者：
Di Liberto D;Locati M;Caccamo N;Vecchi A;Meraviglia S;Salerno A;Sireci G;Nebuloni M;Caceres N;Cardona PJ;Dieli F;Mantovani A
D6 是炎症 CC 趋化因子的诱饵和清道夫受体。通过鼻内给予低剂量的结核分枝杆菌，D6 缺陷小鼠被迅速杀死。 D6−/− 小鼠的死亡与显着的局部和全身炎症反应相关，其结核分枝杆菌集落形成单位的水平与对照 D6 熟练小鼠相似。 D6 缺陷小鼠表现出浸润发炎组织和淋巴结的单核细胞（巨噬细胞、树突状细胞、CD4 和 CD8 T 淋巴细胞）数量增加，CC 趋化因子（CCL2、CCL3、CCL4 和 CCL5）和促炎细胞因子（肿瘤坏死因子 α、 支气管肺泡灌洗液和血清中的白介素 1β 和干扰素 γ）。 D6−/− 感染小鼠中高水平的炎症细胞因子与肝和肾损伤有关，导致肝和肾衰竭。用抗体混合物阻断炎症CC趋化因子逆转了D6−/−小鼠的炎症表型，但导致结核分枝杆菌的生长控制较差。因此，D6 诱饵受体在结核分枝杆菌感染中抗菌素耐药性、免疫激活和炎症之间的平衡中发挥着关键作用。
D6 is a decoy and scavenger receptor for inflammatory CC chemokines. D6-deficient mice were rapidly killed by intranasal administration of low doses of Mycobacterium tuberculosis. The death of D6−/− mice was associated with a dramatic local and systemic inflammatory response with levels of M. tuberculosis colony-forming units similar to control D6-proficient mice. D6-deficient mice showed an increased numbers of mononuclear cells (macrophages, dendritic cells, and CD4 and CD8 T lymphocytes) infiltrating inflamed tissues and lymph nodes, as well as abnormal increased concentrations of CC chemokines (CCL2, CCL3, CCL4, and CCL5) and proinflammatory cytokines (tumor necrosis factor α, interleukin 1β, and interferon γ) in bronchoalveolar lavage and serum. High levels of inflammatory cytokines in D6−/− infected mice were associated with liver and kidney damage, resulting in both liver and renal failure. Blocking inflammatory CC chemokines with a cocktail of antibodies reversed the inflammatory phenotype of D6−/− mice but led to less controlled growth of M. tuberculosis. Thus, the D6 decoy receptor plays a key role in setting the balance between antimicrobial resistance, immune activation, and inflammation in M. tuberculosis infection.
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影响因子：
6
作者：
Nibbs, RJB;Kriehuber, E;Rot, A
通讯作者：
Rot, A
影响因子：
4.4
作者：
Feng, CG;Britton, WJ;Bean, AGD
通讯作者：
Bean, AGD
影响因子：
3.2
作者：
Badewa, AP;Quinton, LJ;Mason, CM
通讯作者：
Mason, CM
影响因子：
6.4
作者：
Kipnis, A;Basaraba, RJ;Cooper, AM
通讯作者：
Cooper, AM
DOI：
10.1073/pnas.0607514104
发表时间：
2007-02-13
影响因子：
11.1
作者：
de la Torre, Yeny Martinez;Buracchi, Chiara;Mantovani, Alberto
通讯作者：
Mantovani, Alberto