Responses of Phagocytic Cells from Inbred Mice to Th1 Cytokines

Objectives: Phagocytic cells are an important first defence line against Candida infections. Th1 cytokines are believed to be able to enhance the efficiency of killing of yeasts by these cells, and our previous study showed that the macrophages and neutrophils of BALB/c mice are able to kill yeasts more efficiently than those from CBA/CaH mice. Accordingly,the aim of this study was to explore the responses of phagocytic cells from two inbred mice, which are genetically susceptible or resistant to candidiasis, to Th1 cytokines. Methods: Inbred female BALB/c and CBA/CaH mice (Animal Center, Perth, Australia) and C. albicans 3630 (AMMRL, Sydney, Australia) were used in this study. Oral infection was established by inoculation of live C. albicans orally, and monitored by swabbing. Neutrophils, macrophages and monocytes were isolated from long and short-term bone marrow culture, and used to estimate the phagocytic cell function to kill the yeasts with FACS (BD, USA). Th1 cytokines included interferon gamma (IFN-ã), tumor necrosis factor alpha (TNF-á) and granulocyte-macrophage colony-stimulating factor (GM-CSF) (Sigma USA) were used as potentiating factors. Results: Mouse IFN-ã, TNF-á and GM-CSF markedly enhanced killing of unopsonised C. albicans 3630 by macrophages from CBA/CaH mice (p<0.01), but had no effect on the enhancement of killing by macrophages from BALB/c mice(p>0.05). A comparison of the killing capacities of neutrophils and monocytes against yeasts demonstrated that monocytes and neutrophils from BALB/c mice are equally capable of killing the yeast (p>0.05), whereas monocytes from CBA/CaH mice killed the yeast more efficiently than did neutrophils (p<0.001). Conclusions: The diversity of responses of phagocytic cells from CBA/CaH and BALB/c to Th1 cytokines may account for the susceptibility to oral infection, and the mechanism should be elucidated.