Contribution of Invariant Natural Killer T Cells to the Clearance of Pseudomonas aeruginosa from Skin Wounds.

Contribution of Invariant Natural Killer T Cells to the Clearance of Pseudomonas aeruginosa from Skin Wounds.
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DOI:
10.3390/ijms22083931
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发表时间:
2021-04-10
影响因子:
5.6
通讯作者:
Kawakami K
Kawakami K
中科院分区:
生物学2区
文献类型:
--
作者:
Tanno H;Kanno E;Sato S;Asao Y;Shimono M;Kurosaka S;Oikawa Y;Ishi S;Shoji M;Sato K;Kasamatsu J;Miyasaka T;Yamamoto H;Ishii K;Imai Y;Tachi M;Kawakami K

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慢性感染被认为是皮肤伤口最严重的问题之一,细菌存在于90%以上的慢性伤口中。铜绿假单胞菌经常从慢性伤口中分离出来,被认为是伤口愈合延迟的原因。不变的自然杀伤T细胞(iNKT)是一种独特的淋巴细胞,在各种炎症反应中具有强大的调节能力,可以加速伤口愈合过程。在本研究中,我们研究了iNKT细胞在宿主防御伤口部位铜绿假单胞菌接种中的作用。我们分析了再上皮化、细菌负荷、白细胞积累、细胞因子和抗菌肽的产生。与野生型(WT)小鼠相比,iNKT细胞缺陷(Jα18KO)小鼠在第7天的再上皮化明显减少,活菌落数量明显增加。第5天,Jα18KO小鼠IL-17A和IL-22的产生明显低于WT小鼠。此外,与WT小鼠相比,给予iNKT细胞特异性激活剂α-半乳糖神经酰胺(α-GalCer)可增强宿主保护,如细菌负荷减少所示,并增加IL-22、IL-23和S100A9的产生。这些结果表明iNKT细胞在皮肤伤口愈合过程中促进铜绿假单胞菌的清除。
Chronic infections are considered one of the most severe problems in skin wounds, and bacteria are present in over 90% of chronic wounds. Pseudomonas aeruginosa is frequently isolated from chronic wounds and is thought to be a cause of delayed wound healing. Invariant natural killer T (iNKT) cells, unique lymphocytes with a potent regulatory ability in various inflammatory responses, accelerate the wound healing process. In the present study, we investigated the contribution of iNKT cells in the host defense against P. aeruginosa inoculation at the wound sites. We analyzed the re-epithelialization, bacterial load, accumulation of leukocytes, and production of cytokines and antimicrobial peptides. In iNKT cell–deficient (Jα18KO) mice, re-epithelialization was significantly decreased, and the number of live colonies was significantly increased, when compared with those in wild-type (WT) mice on day 7. IL-17A, and IL-22 production was significantly lower in Jα18KO mice than in WT mice on day 5. Furthermore, the administration of α-galactosylceramide (α-GalCer), a specific activator of iNKT cells, led to enhanced host protection, as shown by reduced bacterial load, and to increased production of IL-22, IL-23, and S100A9 compared that of with WT mice. These results suggest that iNKT cells promote P. aeruginosa clearance during skin wound healing.
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