Early Activation of iNKT Cells Increased Survival Time of BALB/c Mice in a Murine Model of Melioidosis
Issued Date
2022-12-01
Resource Type
ISSN
00199567
eISSN
10985522
Scopus ID
2-s2.0-85144585130
Pubmed ID
36374098
Journal Title
Infection and Immunity
Volume
90
Issue
12
Rights Holder(s)
SCOPUS
Bibliographic Citation
Infection and Immunity Vol.90 No.12 (2022)
Suggested Citation
Kasetthat T., Kamuthachad L., Sermswan R.W., Watarai H., Matangkasombut P., Wongratanacheewin S. Early Activation of iNKT Cells Increased Survival Time of BALB/c Mice in a Murine Model of Melioidosis. Infection and Immunity Vol.90 No.12 (2022). doi:10.1128/iai.00268-22 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/84836
Title
Early Activation of iNKT Cells Increased Survival Time of BALB/c Mice in a Murine Model of Melioidosis
Other Contributor(s)
Abstract
Melioidosis is an infectious disease caused by Burkholderia pseudomallei. High interferon gamma (IFN-γ) levels in naive mice were reported to mediate protection against B. pseudomallei infection. Invariant natural killer T (iNKT) cells can produce and secrete several cytokines, including IFN-γ. When iNKT cell-knockout (KO) BALB/c mice were infected with B. pseudomallei, their survival time was significantly shorter than wild-type mice. Naive BALB/c mice pretreated intraperitoneally with α-galactosylceramide (α-GalCer), an iNKT cell activator, 24 h before infection demonstrated 62.5% survival at the early stage, with prolonged survival time compared to nonpretreated infected control mice (14 ± 1 days versus 6 ± 1 days, respectively). At 4 h after injection with α-GalCer, treated mice showed significantly higher levels of serum IFN-γ, interleukin-4 (IL-4), IL-10, and IL-12 than control mice. Interestingly, the IFN-γ levels in the α-GalCer-pretreated group were decreased at 4, 24, and 48 h after infection, while they were highly increased in the control group. At 24 h postinfection in the α-GalCer group, bacterial loads were significantly lower in blood (no growth and 1,780.00 6 51.21, P < 0.0001), spleens (no growth and 34,300 ± 1,106.04, P < 0.0001), and livers (1,550 ± 68.72 and 13,400 ± 1,066.67, P < 0.0001) than in the control group, but not in the lungs (15,300 ± 761.10 and 1,320 ± 41.63, P < 0.0001), and almost all were negative at 48 h postinfection. This study for the first time shows that early activation of iNKT cells by a-GalCer helps clearance of B. pseudomallei and prolongs mouse survival.