Role for both myeloid and plasmacytoid DC in driving primary T helper cell response to Burkholderia pseudomallei in healthy individuals

Abstract

AbstractBurkholderia pseudomallei is a Gram-negative bacterium that causes melioidosis, an infectious disease endemic to south-east Asia. As B. pseudomallei is antibiotic-resistant, the need for cell-based vaccines and therapies is crucial to managing melioidosis. Dendritic cells (DC) provide the first line of defense to infection and direct downstream immune responses. Using practical volumes of fresh healthy donor blood, we show that heat-killed B. pseudomallei activated and stimulated expression of pro-inflammatory cytokines TNF-α, IL-1β and IL-6 from both myeloid and plasmacytoid DC. Furthermore, B. pseudomallei-pulsed DC induced activation and proliferation of CD4+ T-cells. Thus, both DC subsets are important for driving primary T helper cell responses to B. pseudomallei in healthy individuals and have the potential to be targeted for future therapies and vaccines.Author SummaryMelioidosis is an infectious disease endemic to south-east Asia and northern Australia caused by the bacterium Burkholderia pseudomallei. Melioidosis presents a significant public health threat because it has no effective vaccine or cure, leading to a high mortality rate of between 10-50%. We highlight the possibility of immune-based strategies targeting Burkholderia pseudomallei to better treat and prevent melioidosis. Specifically, we show that dendritic cells-the sentinel cells of the immune system-respond to B. pseudomallei in healthy individuals and in turn can orchestrate downstream protective immune responses. Thus, dendritic cells may be key players in the development of both vaccines and therapeutics for melioidosis as well as other bacteria-driven diseases.