title: Induction of multiple chemokine and colony-stimulating factor genes in experimental Burkholderia pseudomallei infection.
abstract: Melioidosis is a disease of the tropics caused by the facultative intracellular bacterium Burkholderia pseudomallei. In human infection, increased levels of IFN-gamma in addition to the chemokines interferon-gamma-inducible protein 10 (IP-10) and monocyte interferon-gamma-inducible protein (Mig) have been demonstrated. However, the role of these and other chemokines in the pathogenesis of melioidosis remains unknown. Using BALB/c and C57BL/6 mice as models of the acute and chronic forms of human melioidosis, the induction 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 similar in liver and spleen; however, responses were typically greater in spleen, which reflected higher tissue bacterial loads. In BALB/c mice, high-level expression of mRNA for all chemokines and CSF investigated was demonstrated at day 3 postinfection, correlating with peak bacterial load and extensive infiltration of leucocytes. In contrast, increased mRNA expression and bacterial numbers in C57BL/6 mice were greatest between 4 and 14 days following infection. This paralleled increases in the size and number of abscesses in liver and spleen of C57BL/6 mice at days 3 and 14 postinfection. Earlier induction of cytokine-induced neutrophil chemoattractant (KC), macrophage inflammatory protein-2 (MIP-2), monocyte chemoattractant protein-1 (MCP-1), granulocyte-macrophage CSF (GM-CSF) and macrophage CSF (M-CSF) mRNA was demonstrated in spleen, while MIP-2, MCP-1, IP-10 and Mig were demonstrated in liver of BALB/c mice when compared to spleen and liver of C57BL/6. The magnitude of cellular responses observed in the tissue correlated with increased 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 lesions in C57BL/6 mice predominantly comprised macrophages. These results suggest that the inability of BALB/c mice to contain the infection at sites of inflammation may underlie the susceptible phenotype of this mouse strain towards B. pseudomallei infection.
authors.affiliation: School of Biomedical Science, James Cook University, Townsville, Queensland, Australia. jodie.barnes@jcu.edu.au
authors.forename: J L
authors.initials: JL
authors.lastname: Barnes
authors.forename: G C
authors.initials: GC
authors.lastname: Ulett
authors.forename: N
authors.initials: N
authors.lastname: Ketheesan
authors.forename: T
authors.initials: T
authors.lastname: Clair
authors.forename: P M
authors.initials: PM
authors.lastname: Summers
authors.forename: R G
authors.initials: RG
authors.lastname: Hirst
mesh_terms: D000818:Animals; D016957:Burkholderia pseudomallei / Q000254:growth & development / Q000276:immunology* / Q000502:physiology; D018925:Chemokines / Q000235:genetics* / Q000378:metabolism; D003115:Colony-Stimulating Factors / Q000235:genetics* / Q000378:metabolism; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D006801:Humans; D008099:Liver / Q000276:immunology / Q000382:microbiology; D008554:Melioidosis / Q000235:genetics / Q000276:immunology* / Q000382:microbiology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013154:Spleen / Q000276:immunology / Q000382:microbiology
chemical_list: D018925:Chemokines; D003115:Colony-Stimulating Factors; D012333:RNA, Messenger