Nitric oxide prevents a pathogen-permissive granulocytic inflammation during tuberculosis.
Nitric oxide prevents a pathogen-permissive granulocytic inflammation during tuberculosis.
复制标题
一氧化氮可预防结核病期间病原体允许的粒细胞炎症
DOI：
10.1038/nmicrobiol.2017.72
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发表时间：
2017-05-15
影响因子：
28.3
通讯作者：
Sassetti CM
中科院分区：
文献类型：
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作者：
Mishra BB;Lovewell RR;Olive AJ;Zhang G;Wang W;Eugenin E;Smith CM;Phuah JY;Long JE;Dubuke ML;Palace SG;Goguen JD;Baker RE;Nambi S;Mishra R;Booty MG;Baer CE;Shaffer SA;Dartois V;McCormick BA;Chen X;Sassetti CM
一氧化氮（NO）有助于预防结核病（TB）。通常认为这种保护作用是由于直接抑制结核杆菌（Mtb）的生长，从而防止随后的病理性炎症。相反，我们报告NO主要通过抑制白细胞介素-1和12/15-脂氧合酶依赖性中性粒细胞募集级联反应来保护小鼠，该级联反应促进细菌复制。使用Mtb突变体作为病原体环境的指标，我们推断粒细胞炎症会产生一个支持Mtb生长的营养丰富的生态位。平行的临床研究表明，类似的炎症途径促进了患者的结核病。人12/15脂氧合酶直系同源物ALOX 12在空洞性TB病变中表达，其产物的丰度与气道中性粒细胞的数量和细菌负荷相关，并且增加ALOX 12表达的遗传多态性与TB风险相关。这些数据表明，结核分枝杆菌利用嗜酸性炎症优先在促进传染的组织损伤部位复制。
Nitric oxide (NO) contributes to protection from tuberculosis (TB). It is generally assumed that this protection is due to direct inhibition of Mycobacterium tuberculosis (Mtb) growth, which prevents subsequent pathological inflammation. In contrast, we report NO primarily protects mice by repressing an interleukin-1 and 12/15-lipoxygenase dependent neutrophil recruitment cascade that promotes bacterial replication. Using Mtb mutants as indicators of the pathogen's environment, we inferred that granulocytic inflammation generates a nutrient-replete niche that supports Mtb growth. Parallel clinical studies indicate that a similar inflammatory pathway promotes TB in patients. The human 12/15 lipoxygenase ortholog, ALOX12, is expressed in cavitary TB lesions, the abundance of its products correlate with the number of airway neutrophils and bacterial burden, and a genetic polymorphism that increases ALOX12 expression is associated with TB risk. These data suggest that Mtb exploits neutrophilic inflammation to preferentially replicate at sites of tissue damage that promote contagion.