The innate interferon gamma response of BALB/c and C57BL/6 mice to in vitro Burkholderia pseudomallei infection

Na？ve BALB/c splenocytes were found to produce more IFN-γ in response to live bacterial infection compared to C57BL/6 splenocytes. Natural killer cells were found to be the major producers of IFN-γ, while T cells and Gr-1intermediate cells also contributed to the IFN-γ response. Although anti-Gr-1 depletion substantially reduced the IFN-γ 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-γ between BALB/c and C57BL/6 splenocytes. Although IL-12 is essential for the IFN-γ 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-1β, TNF-α, IL-6, IL-18 than C57BL/6 splenocytes after infection with B. pseudomallei.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-γ hyperproduction in BALB/c mice.Burkholderia pseudomallei is the causative agent for melioidosis, an infectious disease endemic in South-east Asia and northern Australia [1,2]. It has also been increasingly reported in other tropical and subtropical regions [3]. The bacillus is a facultative intracellular microbe and can invade and replicate in many different organs. Infection can result in a wide spectrum of clinical outcomes, ranging from an asymptomatic state, benign pulmonitis, acute or chronic pneumonia, and to fulminant septicemias [4]. Furthermore, even after the apparent resolution of acute symptoms, the infection can persist for decades as a chronic and latent condition where relapse is possible [5]. Despite appropriate antibiotic treatment, severe melioidosis with acute septicemia is associated with a high mortality rate [6].In severe melioidosis, patients exhibit elevated serum levels of proinflammatory cytokines such as TNF-α [7], IFN-γ [8] and IFN-γ induced chemokines IP-10 and MIG [9]. Mur