Aggregatibacter actinomycetemcomitans Leukotoxin: A Powerful Tool with Capacity to Cause Imbalance in the Host Inflammatory Respeonse
Aggregatibacter actinomycetemcomitans Leukotoxin: A Powerful Tool with Capacity to Cause Imbalance in the Host Inflammatory Respeonse
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DOI：
10.3390/toxins3030242
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发表时间：
2011-03-01
期刊：
影响因子：
4.2
通讯作者：
Johansson, Anders
中科院分区：
文献类型：
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作者：
Johansson, Anders
伴放线菌聚集杆菌是人类口腔固有菌群的一员，参与牙周炎和各种非口腔感染的病理过程。这种细菌通过表达白细胞毒素选择性地杀死人类白细胞，白细胞毒素是一种属于毒素重复序列（RTX）家族的大孔形成蛋白。毒素的特异性与其特异性靶细胞受体LFA-1的先决条件有关，LFA-1仅在白细胞上表达。白细胞毒素以多种方式引起不同白细胞群体的死亡。它激活从中性粒细胞快速释放溶酶体酶和MMP，并引起淋巴细胞凋亡。在单核细胞/巨噬细胞中，毒素激活半胱氨酸蛋白酶-1，半胱氨酸蛋白酶-1通过激活和分泌IL-1 β和IL-18引起促炎反应。将A.白细胞毒素表达增强的伴放线菌与感染个体的疾病发作显著相关。总之，这种毒素杀死白细胞的机制与炎症性疾病（如牙周炎）的致病机制密切相关。针对牙周病的细胞和分子炎症宿主反应的治疗策略可能是未来的治疗选择。
Aggregatibacter actinomycetemcomitans has been described as a member of the indigenous oral microbiota of humans, and is involved in the pathology of periodontitis and various non-oral infections. This bacterium selectively kills human leukocytes through expression of leukotoxin, a large pore-forming protein that belongs to the Repeat in Toxin (RTX) family. The specificity of the toxin is related to its prerequisite for a specific target cell receptor, LFA-1, which is solely expressed on leukocytes. The leukotoxin causes death of different leukocyte populations in a variety of ways. It activates a rapid release of lysosomal enzymes and MMPs from neutrophils and causes apoptosis in lymphocytes. In the monocytes/macrophages, the toxin activates caspase-1, a cysteine proteinase, which causes a proinflammatory response by the activation and secretion of IL-1 beta and IL-18. A specific clone (JP2) of A. actinomycetemcomitans with enhanced leukotoxin expression significantly correlates to disease onset in infected individuals. Taken together, the mechanisms by which this toxin kills leukocytes are closely related to the pathogenic mechanisms of inflammatory disorders, such as periodontitis. Therapeutic strategies targeting the cellular and molecular inflammatory host response in periodontal diseases might be a future treatment alternative.