Role of T Cells in Innate and Adaptive Immunity against MurineBurkholderia pseudomalleiInfection

Abstract

Antigen-specific T cells are important sources of interferon (IFN)-gamma for acquired immunity to intracellular pathogens, but they can also produce IFN- gamma directly via a "bystander" activation pathway in response to proinflammatory cytokines. We investigated the in vivo role of cytokine- versus antigen-mediated T cell activation in resistance to the pathogenic bacterium Burkholderia pseudomallei. IFN-gamma, interleukin (IL)-12, and IL-18 were essential for initial bacterial control in infected mice. B. pseudomallei infection rapidly generated a potent IFN-gamma response from natural killer (NK) cells, NK T cells, conventional T cells, and other cell types within 16 h after infection, in an IL-12- and IL-18-dependent manner. However, early T cell- and NK cell-derived IFN-gamma responses were functionally redundant in cell depletion studies, with IFN-gamma produced by other cell types, such as major histocompatibility complex class II(int) F4/80(+) macrophages being sufficient for initial resistance. In contrast, B. pseudomallei-specific CD4(+) T cells played an important role during the later stage of infection. Thus, the T cell response to primary B. pseudomallei infection is biphasic, an early cytokine-induced phase in which T cells appear to be functionally redundant for initial bacterial clearance, followed by a later antigen-induced phase in which B. pseudomallei-specific T cells, in particular CD4(+) T cells, are important for host resistance.

Glutathione deficiency in type 2 diabetes impairs cytokine responses and control of intracellular bacteria

“…Differences in signaling from other cell types could also accentuate the differential IL-12 production. It has been documented that B. pseudomallei infection induced early IFN-γ production by NK cells and bystander T cells with memory phenotype both in mice and humans (35)(36)(37). These early sources of IFN-γ represent the priming signals in our monocyte model, necessary to help monocytes produce IL-12 when triggered by bacterial infection.…”

Heme Oxygenase-1 and Carbon Monoxide PromoteBurkholderia pseudomalleiInfection

“…Lymphocytes from spleen were prepared using modified protocols as previously described (35). Spleens were removed and splenocyte suspensions were produced by passing them through sterile 70-mm cell strainers.…”

Interaction of Burkholderia pseudomallei and Burkholderia thailandensis with human monocyte-derived dendritic cells

“…A strong IFN-c response is believed to be essential for clearance of B. pseudomallei (Barnes et al, 2004;Haque et al, 2006). The production of IFN-c is the hallmark of a cellular Th1-type immune response, which is typically mediated by production of IL-12 by DCs (Heufler et al, 1996).…”

“…The disease is more prevalent in individuals with predisposing conditions such as diabetes mellitus or renal disease, and both disease initiation and outcome of infection with B. pseudomallei are largely dependent on the host immune response. A strong cell-mediated immune response with production of interferon gamma (IFN-c) is known to be important in protection from primary infection in mice (Haque et al, 2006) and is also believed to be important in protecting against human infection (Tippayawat et al, 2009). …”