TY - JOUR
T1 - Contribution of invariant natural killer t cells to the clearance of pseudomonas aeruginosa from skin wounds
AU - Tanno, Hiromasa
AU - Kanno, Emi
AU - Sato, Suzuna
AU - Asao, Yu
AU - Shimono, Mizuki
AU - Kurosaka, Shiho
AU - Oikawa, Yukari
AU - Ishi, Shinyo
AU - Shoji, Miki
AU - Sato, Ko
AU - Kasamatsu, Jun
AU - Miyasaka, Tomomitsu
AU - Yamamoto, Hideki
AU - Ishii, Keiko
AU - Imai, Yoshimichi
AU - Tachi, Masahiro
AU - Kawakami, Kazuyoshi
N1 - Funding Information:
Funding: This work was supported in part by a Grant-in-Aid for Scientific Research (B) (19H03918), a Grant-in-Aid for Challenging Exploratory Research (17K19710), and a Grant-in-Aid for Young Scientists (17K17393 and 19K19494) from the Ministry of Education, Culture, Sports, Science and Technology of Japan.
Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2021/4/2
Y1 - 2021/4/2
N2 - 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.
AB - 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.
KW - Antimicrobial peptide
KW - IFN-γ
KW - IL-17A
KW - IL-22
KW - INKT cell
KW - Pseudomonas aeruginosa
KW - Skin wound healing
UR - http://www.scopus.com/inward/record.url?scp=85103851162&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85103851162&partnerID=8YFLogxK
U2 - 10.3390/ijms22083931
DO - 10.3390/ijms22083931
M3 - Article
C2 - 33920301
AN - SCOPUS:85103851162
SN - 1422-0067
VL - 22
JO - International Journal of Molecular Sciences
JF - International Journal of Molecular Sciences
IS - 8
M1 - 3931
ER -