title: Protective cellular responses to Burkholderia mallei infection.
abstract: Burkholderia mallei is a Gram-negative bacillus causing the disease glanders in humans. During intraperitoneal infection, BALB/c mice develop a chronic disease characterised by abscess formation where mice normally die up to 70 days post-infection. Although cytokine responses have been investigated, cellular immune responses to B. mallei infection have not previously been characterised. Therefore, the influx and activation status of splenic neutrophils, macrophages and T cells was examined during infection. Gr-1+ neutrophils and F4/80+ macrophages infiltrated the spleen 5 h post-infection and an increase in activated macrophages, neutrophils and T cells occurred by 24 h post-infection. Mice depleted of Gr-1+ cells were acutely susceptible to B. mallei infection, succumbing to the infection 5 days post-infection. Mice depleted of both CD4 and CD8 T cells did not succumb to the infection until 14 days post-infection. Infected μMT (B cell) and CD28 knockout mice did not differ from wildtype mice whereas iNOS-2 knockout mice began to succumb to the infection 30 days post-infection. The data presented suggests that Gr-1+ cells, activated early in B. mallei infection, are essential for controlling the early, innate response to B. mallei infection and T cells or nitric oxide are important during the later stages of infection.
authors.affiliation: Dstl, Biomedical Sciences, Porton Down, Salisbury SP40JQ, UK. carowland@dstl.gov.uk
authors.forename: Caroline A
authors.initials: CA
authors.lastname: Rowland
authors.forename: M Stephen
authors.initials: MS
authors.lastname: Lever
authors.forename: Kate F
authors.initials: KF
authors.lastname: Griffin
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Bancroft
authors.forename: Roman A
authors.initials: RA
authors.lastname: Lukaszewski
mesh_terms: D000818:Animals; D042726:Burkholderia mallei / Q000276:immunology*; D004195:Disease Models, Animal; D005260:Female; D005896:Glanders / Q000276:immunology*; D007274:Injections, Intraperitoneal; D047589:Leukocyte Reduction Procedures; D008264:Macrophages / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009504:Neutrophils / Q000276:immunology*; D009569:Nitric Oxide / Q000276:immunology; D013154:Spleen / Q000276:immunology; D016019:Survival Analysis; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D009569:Nitric Oxide