title: Sublethal doses of anthrax lethal toxin on the suppression of macrophage phagocytosis.
abstract: BACKGROUND
  Lethal toxin (LT), the major virulence factor produced by Bacillus anthracis, has been shown to suppress the immune system, which is beneficial to the establishment of B. anthracis infections. It has been suggested that the suppression of MEK/MAPK signaling pathways of leukocytes contributes to LT-mediated immunosuppressive effects. However, the involvement of MAPK independent pathways has not been clearly elucidated; nor has the crucial role played by LT in the early stages of infection. Determining whether LT exerts any pathological effects before being enriched to an MEK inhibitory level is an important next step in the furtherance of this field.
  
  
  RESULTS
  Using a cell culture model, we determined that low doses of LT inhibited phagocytosis of macrophages, without influencing MAPK pathways. Consistent low doses of LT significantly suppressed bacterial clearance and enhanced the mortality of mice with bacteremia, without suppressing the MEK1 of splenic and peripheral blood mononuclear cells.
  
  
  CONCLUSIONS
  These results suggest that LT suppresses the phagocytes in a dose range lower than that required to suppress MEK1 in the early stages of infection.
authors.affiliation: Institute of Preventive Medicine, National Defense Medical Center, Taipei, Taiwan, Republic of China.
authors.forename: Jyh-Hwa
authors.initials: JH
authors.lastname: Kau
authors.forename: Der-Shan
authors.initials: DS
authors.lastname: Sun
authors.forename: Hsuan-Shun
authors.initials: HS
authors.lastname: Huang
authors.forename: Te-Sheng
authors.initials: TS
authors.lastname: Lien
authors.forename: Hsin-Hsien
authors.initials: HH
authors.lastname: Huang
authors.forename: Hung-Chi
authors.initials: HC
authors.lastname: Lin
authors.forename: Hsin-Hou
authors.initials: HH
authors.lastname: Chang
mesh_terms: D000818:Animals; D000942:Antigens, Bacterial / Q000378:metabolism*; D001408:Bacillus anthracis / Q000276:immunology; D001427:Bacterial Toxins / Q000378:metabolism*; D005434:Flow Cytometry / Q000379:methods; D007166:Immunosuppressive Agents / Q000378:metabolism; D007962:Leukocytes / Q000166:cytology; D007963:Leukocytes, Mononuclear / Q000378:metabolism / Q000382:microbiology; D048369:MAP Kinase Kinase 1 / Q000378:metabolism; D008264:Macrophages / Q000276:immunology* / Q000378:metabolism* / Q000382:microbiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008954:Models, Biological; D010587:Phagocytosis; D018805:Sepsis / Q000382:microbiology
chemical_list: D000942:Antigens, Bacterial; D001427:Bacterial Toxins; D007166:Immunosuppressive Agents; C030325:anthrax toxin; D048369:MAP Kinase Kinase 1