Burkholderia pseudomallei is the causative agent of melioidosis. While adaptive immunity has been shown to be important for host resistance to B. pseudomallei, the direct interaction of the bacteria with adaptive immune cells such as T and B cells is not well known. To address this question, we infected Jurkat T cells, as well as human primary CD4؉ and CD8 ؉ T cells, with live B. pseudomallei. We found that live bacterial infection could costimulate T cells to produce interleukin-2 (IL-2) and gamma interferon (IFN-␥) in the presence of anti-CD3 cross-linking antibodies. Bacterial supernatant could also costimulate T cells, and this was due to the presence of flagellin in the supernatant. However, T cells infected with bacterial mutants lacking flagellin showed strong impairment in IL-2 but only a slight impairment in IFN-␥ production. When cross-linking of CD3 is replaced by IL-2, live bacterial infection was still able to costimulate human primary T cells to produce IFN-␥ and flagellin is only a minor ligand contributing to this costimulation. Thus, live B. pseudomallei could potentially costimulate T cells not only in an antigen-specific manner but also in a nonspecific manner through bystander activation via IL-2.Burkholderia pseudomallei is a gram-negative bacterium responsible for causing melioidosis, an infectious disease endemic in Southeast Asia and Northern Australia. The bacterium can invade and replicate in both cultured phagocytic (18, 28) and nonphagocytic cells (19). The type III secretion system 3 (TTSS3), also known as the Burkholderia secretion apparatus, enables B. pseudomallei to escape from the endosome into the cytoplasm of infected cells (29). Furthermore, the BimA protein found on one pole of the bacteria helps to facilitate intracellular spread by the formation of actin comet tails (30). These characteristics of the bacterium could help it to survive intracellularly. Upon phagocytosis by macrophages, B. pseudomallei is able to activate the suppressor of cytokine signaling 3 (SOCS3) and cytokine-inducible Src homology 2-containing protein, resulting in a decrease in the gamma interferon (IFN-␥) signaling response (9). We had previously shown that B. pseudomallei infection of monocytes, macrophages, and dendritic cells induced caspase-1-dependent cell death (32). The interference with host innate immune cells such as macrophages could have a profound impact on the innate immune response to bacteria, as well as on the development of the adaptive immune response.The interaction of B. pseudomallei with other immune cells, particularly those from the adaptive immune response such as T and B cells, is not well known. It has been shown that patients surviving melioidosis developed a cell-mediated immune response (20) and, in mice, B. pseudomallei-specific CD4 T cells are important for host resistance in adaptive immunity (16). This means that the ability of the host to develop a robust T-cell response is likely critical in controlling the infection, and there is a possibility that bacteria could ...
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