Role of T cells in innate and adaptive immunity against murine Burkholderia pseudomallei infection

J Infect Dis. 2006 Feb 1;193(3):370-9. doi: 10.1086/498983. Epub 2005 Dec 27.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Burkholderia pseudomallei / immunology*
  • Cytokines / metabolism
  • Female
  • Humans
  • Interferon-gamma / biosynthesis*
  • Killer Cells, Natural / immunology
  • Killer Cells, Natural / metabolism
  • Melioidosis / immunology*
  • Melioidosis / microbiology
  • Mice
  • Mice, Inbred C57BL
  • Specific Pathogen-Free Organisms
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / metabolism


  • Cytokines
  • Interferon-gamma