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Published on: October 15, 2013
Plasmacytoid dendritic cell bactericidal activity against Burkholderia pseudomallei
Natasha L Williams1, Jodie L Morris1, Catherine M Rush1
1Australian Institute of Tropical Health and Medicine, College of Public Health, Medicine and Veterinary Sciences, James Cook University, Townsville, Queensland 4811, Australia.
Abstract:
Melioidosis sepsis, caused by Burkholderia pseudomallei, is associated with high mortality due to an overwhelming inflammatory response. Plasmacytoid dendritic cells (pDC) are potent producers of type I interferons (IFN). This study investigated whether pDC and type I IFN play a role during the early stages of B. pseudomallei infection. Human and murine pDC internalised and killed B. pseudomallei as efficiently as murine conventional DC (cDC). pDC derived from B. pseudomallei-susceptible (BALB/c) mice demonstrated poor intracellular killing and increased IFN-alpha compared to pDC derived from B. pseudomallei-resistant (C57BL/6) mice. This is the first evidence of pDC bactericidal activity against B. pseudomallei infection.
Insights
Plasmacytoid dendritic cells (pDC) can internalize and kill Burkholderia pseudomallei, the bacterium causing melioidosis sepsis. This study reveals pDC bactericidal activity, offering new insights into early infection stages.
Area of Science:
- Immunology
- Microbiology
- Infectious Diseases
Background:
- Melioidosis sepsis, caused by Burkholderia pseudomallei, presents a high mortality rate due to severe inflammatory responses.
- Plasmacytoid dendritic cells (pDC) are recognized as significant producers of type I interferons (IFN).
Purpose of the Study:
- To investigate the role of pDC and type I IFN during the initial phases of B. pseudomallei infection.
- To determine the bactericidal capacity of pDC against B. pseudomallei.
Main Methods:
- Comparative analysis of B. pseudomallei internalization and killing by human and murine pDC versus murine conventional DC (cDC).
- Assessment of pDC function in B. pseudomallei-susceptible (BALB/c) and B. pseudomallei-resistant (C57BL/6) mouse models.
Main Results:
- Human and murine pDC exhibited efficient internalization and killing of B. pseudomallei, comparable to murine cDC.
- pDC from susceptible BALB/c mice showed impaired intracellular killing and elevated IFN-alpha production compared to pDC from resistant C57BL/6 mice.
Conclusions:
- This research provides the first evidence of pDC possessing bactericidal activity against B. pseudomallei.
- The findings suggest a differential role for pDC in melioidosis pathogenesis, influenced by host susceptibility and IFN-alpha production.
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