The innate interferon gamma response of BALB/c and C57BL/6 mice to in vitro Burkholderia pseudomallei infection.
BACKGROUND
Burkholderia pseudomallei is the causative agent for melioidosis. For many bacterial infections, cytokine dysregulation is one of the contributing factors to the severe clinical outcomes in the susceptible hosts. The C57BL/6 and BALB/c mice have been established as a differential model of susceptibility in murine melioidosis. In this study, we compared the innate IFN-gamma response to B. pseudomallei between the C57BL/6 and BALB/c splenocytes and characterized the hyperproduction of IFN-gamma in the relatively susceptible BALB/c mice in vitro.


RESULTS
Naïve BALB/c splenocytes were found to produce more IFN-gamma in response to live bacterial infection compared to C57BL/6 splenocytes. Natural killer cells were found to be the major producers of IFN-gamma, while T cells and Gr-1intermediate cells also contributed to the IFN-gamma response. Although anti-Gr-1 depletion substantially reduced the IFN-gamma response, this was not due to the contribution of Gr-1high, Ly-6G expressing neutrophils. We found no differences in the cell types making IFN-gamma between BALB/c and C57BL/6 splenocytes. Although IL-12 is essential for the IFN-gamma response, BALB/c and C57BL/6 splenocytes made similar amounts of IL-12 after infection. However, BALB/c splenocytes produced higher proinflammatory cytokines such as IL-1beta, TNF-alpha, IL-6, IL-18 than C57BL/6 splenocytes after infection with B. pseudomallei.


CONCLUSIONS
Higher percentages of Gr-1 expressing NK and T cells, poorer ability in controlling bacteria growth, and higher IL-18 could be the factors contributing to IFN-gamma hyperproduction in BALB/c mice.
Koo
Ghee Chong
GC
Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, MD7, 8 Medical Drive, Singapore 117597, Republic of Singapore. medp1142@nus.edu.sg
Gan
Yunn-Hwen
YH
D000818:Animals; D016957:Burkholderia pseudomallei / Q000276:immunology*; D002478:Cells, Cultured; D006801:Humans; D007113:Immunity, Innate / Q000276:immunology*; D007371:Interferon-gamma / Q000096:biosynthesis / Q000276:immunology*; D007378:Interleukins / Q000096:biosynthesis; D008554:Melioidosis / Q000276:immunology* / Q000382:microbiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009504:Neutrophils / Q000378:metabolism; D019707:Receptors, Chemokine / Q000378:metabolism; D013154:Spleen / Q000276:immunology / Q000378:metabolism
C503133:Gr-1 protein, mouse; D007378:Interleukins; D019707:Receptors, Chemokine; D007371:Interferon-gamma