Induction of multiple chemokine and colony-stimulating factor genes in experimental Burkholderia pseudomallei infection

Melioidosis is a disease of the tropics caused by the facultative intracell ular bacterium Burkholderia pseudomallei. In human infection, increased lev els of IFN-gamma in addition to the chemokines interferon-gamma -inducible protein 10 (IP-10) and monocyte interferon-gamma -inducible protein (Mig) h ave been demonstrated. However, the role of these and other chemokines in t he pathogenesis of melioidosis remains unknown. Using BALB/c and C57BL/6 mi ce as models of the acute and chronic forms of human melioidosis, the induc tion of mRNA was assessed for various chemokines and CSF (G-CSF, M-CSF, GM- CSF, IP-10, Mig, RANTES, MCP-1, KC and MIP-2) in spleen and liver following B. pseudomallei infection. Patterns of chemokine and CSF induction were si milar in liver and spleen; however, responses were typically greater in spl een, which reflected higher tissue bacterial loads. In BALB/c mice, high-le vel expression of mRNA for all chemokines and CSF investigated was demonstr ated at day 3 postinfection, correlating with peak bacterial load and exten sive infiltration of leucocytes. In contrast, increased mRNA expression and bacterial numbers in C57BL/6 mice were greatest between 4 and 14 days foll owing infection. This paralleled increases in the size and number of absces ses in liver and spleen of C57BL/6 mice at days 3 and 14 postinfection. Ear lier induction of cytokine-induced neutrophil chemoattractant (KC), macroph age inflammatory protein-2 (MIP-2), monocyte chemoattractant protein-1 (MCP -1), granulocyte-macrophage CSF (GM-CSF) and macrophage CSF (M-CSF) mRNA wa s demonstrated in spleen, while MIP-2, MCP-1, IP-10 and Mig were demonstrat ed in liver of BALB/c mice when compared to spleen and liver of C57BL/6. Th e magnitude of cellular responses observed in the tissue correlated with in creased levels of the chemokines and CSF investigated, as well as bacterial load. Compared with C57BL/6 mice, greater infiltration of neutrophils was observed in liver and spleen of BALB/c mice at day 3. In contrast, early le sions in C57BL/6 mice predominantly comprised macrophages. These results su ggest that the inability of BALB/c mice to contain the infection at sites o f inflammation may underlie the susceptible phenotype of this mouse strain towards B. pseudomallei infection.