Abstract
Melioidosis is a disease in tropical and subtropical regions of the world that is caused by Burkholderia pseudomallei. In endemic regions the disease occurs primarily in humans and goats. In the present study, we used the goat as a model to dissect the polar lipids of B. pseudomallei to identify lipid molecules that could be used for adjuvants/vaccines or as diagnostic tools. We showed that the lipidome of B. pseudomallei and its fractions contain several polar lipids with the capacity to elicit different immune responses in goats, namely rhamnolipids and ornithine lipids which induced IFN-γ, whereas phospholipids and an undefined polar lipid induced strong IL-10 secretion in CD4+ T cells. Autologous T cells co-cultured with caprine dendritic cells (cDCs) and polar lipids of B. pseudomallei proliferated and up-regulated the expression of CD25 (IL-2 receptor) molecules. Furthermore, we demonstrated that polar lipids were able to up-regulate CD1w2 antigen expression in cDCs derived from peripheral blood monocytes. Interestingly, the same polar lipids had only little effect on the expression of MHC class II DR antigens in the same caprine dendritic cells. Finally, antibody blocking of the CD1w2 molecules on cDCs resulted in decreased expression for IFN-γ by CD4+ T cells. Altogether, these results showed that polar lipids of B. pseudomallei are recognized by the caprine immune system and that their recognition is primarily mediated by the CD1 antigen cluster.
Highlights
Interest in the pathogenesis of infection with Burkholderia pseudomallei, the causative agent of melioidosis, and the related pathogen B. mallei which causes glanders disease, has substantially increased following their classification in the United States as category B priority and more recently Tier 1 pathogens with biothreat potential
In this study we demonstrated that polar lipids of B. pseudomallei presented by caprine dendritic cells (DC) can elicit immune T cell responses and that CD1w2 (CD1b antigens in humans) antigens participate in this process
While it has been long recognized that bacterial lipids are excellent diagnostic markers, we and others have demonstrated that bacterial polar lipids can stimulate specific immune responses in the host [24,31]
Summary
Interest in the pathogenesis of infection with Burkholderia pseudomallei, the causative agent of melioidosis, and the related pathogen B. mallei which causes glanders disease, has substantially increased following their classification in the United States as category B priority and more recently Tier 1 pathogens with biothreat potential. While melioidosis has traditionally been recognized as an endemic disease in Southeast Asia and Northern Australia, it is increasingly diagnosed in other tropical and subtropical regions of the world, including South and Central America, Africa and and the Indian subcontinent [1,2,3,4]. These findings are consistent with the notion that melioidosis is greatly under- or misdiagnosed and probably endemic throughout most of the subtropical and tropical regions of the world. New strategies for diagnostics, therapeutics, and vaccines are needed
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