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Invariant Natural Killer T (iNKT) cells response in human melioidosis
Ludthawun Kamuthachad1,2, Pornrith Pisuttimarn3, Thitinan Kasetthat1,2
1Department of Microbiology, Faculty of Medicine, Khon Kaen University, Thailand.
Background:
Melioidosis is an infectious disease caused by Burkholderia pseudomallei. In infected mice, IFN-γ can provide protection against B. pseudomallei infection. Invariant Natural Killer T (iNKT) cells are a subpopulation of T lymphocytes, activated by recognition of glycolipid ligands such as α-Galactosylceramide presented by CD1d, produce and secrete several cytokines, including IFN-γ and IL-4. The response of iNKT cells in human melioidosis was then investigated.
Objective:
To determine the iNKT cells response in human melioidosis.
Methods:
The number of human iNKT cells and its activation states were investigated in sepsis melioidosis patients compared with healthy controls using flow cytometry. The iNKT cells activation was confirmed in vitro using heatkilled B. pseudomallei with normal peripheral blood mononuclear cells. The components induced iNKT cell were also determined using different concentration of B. pseudomallei lipopolysaccharide (LPS), heat-killed B. pseudomallei treated with or without DNase, RNase, or proteinase.
Results:
The number of human iNKT cells was significantly lower while the percentage of activated iNKT cells was higher in sepsis melioidosis when compared to control. In addition, B. pseudomallei can stimulate human iNKT cells in vitro. Heat-killed B. pseudomallei could activate iNKT cells but not relate to nucleic acid, proteins, or LPS.
Conclusions:
We found for the first time that the iNKT cells were activated during B. pseudomallei infection in human. However, the roles and the mechanism of iNKT cells during early state of infection needed to be further investigated.
Insights
Invariant Natural Killer T (iNKT) cells are activated during Burkholderia pseudomallei infection in humans. Their exact role and mechanism in early melioidosis require further investigation.
Area of Science:
- Immunology
- Infectious Diseases
Background:
- Melioidosis is caused by Burkholderia pseudomallei.
- Invariant Natural Killer T (iNKT) cells are T lymphocytes that produce cytokines like IFN-γ.
- IFN-γ shows protective effects against B. pseudomallei in mice.
Purpose of the Study:
- To investigate the response of iNKT cells in human melioidosis.
Main Methods:
- Flow cytometry was used to analyze iNKT cell numbers and activation in melioidosis patients versus controls.
- In vitro experiments confirmed iNKT cell activation by heat-killed B. pseudomallei.
- Components inducing iNKT cell activation were explored using bacterial lipopolysaccharide (LPS) and treated bacterial components.
Main Results:
- Human iNKT cell numbers were lower, but activation percentages were higher in melioidosis patients.
- B. pseudomallei directly stimulates human iNKT cells in vitro.
- Activation was induced by heat-killed bacteria, independent of nucleic acids, proteins, or LPS.
Conclusions:
- This study provides the first evidence of iNKT cell activation during human B. pseudomallei infection.
- Further research is needed to elucidate the roles and mechanisms of iNKT cells in early melioidosis stages.
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