title: Effects of the hindlimb-unloading model of spaceflight conditions on resistance of mice to infection with Klebsiella pneumoniae.
abstract: BACKGROUND
  It has been well documented in several studies that many immunologic parameters are altered in experimental animals and human subjects who have flown in space. However, it is not fully known whether these immunologic changes could result in increased susceptibility to infection. Hindlimb (antiorthostatic) unloading of rodents has been used successfully to simulate some of the effects of spaceflight on physiologic systems.
  
  
  OBJECTIVE
  The objective of this study was to determine the effect of hindlimb unloading on the outcome of Klebsiella pneumoniae infection in mice.
  
  
  METHODS
  Hindlimb-unloaded, hindlimb-restrained, and control mice were intraperitoneally infected with one 50% lethal dose of K pneumoniae 2 days after suspension. Mortality and bacterial load in several organs were compared among the groups.
  
  
  RESULTS
  Unloaded mice showed significantly increased mortality and reduced mean time to death compared with that seen in the control groups. Kinetics of bacterial growth with smaller infective doses revealed that control mice were able to clear bacteria from the organs after 30 hours. In contrast, unloaded mice had continued bacterial growth at the same time point.
  
  
  CONCLUSIONS
  The results of this study suggest that hindlimb unloading might enhance the dissemination of K pneumoniae, leading to increased mortality. The complex physiologic changes observed during hindlimb unloading, including stress, have a key role in the pathophysiology of this infection.
authors.affiliation: Department of Microbiology, Biochemistry, and Immunology, Morehouse School of Medicine, 720 Westview Drive SW, Atlanta, GA 30310-1495.
authors.forename: Tesfaye
authors.initials: T
authors.lastname: Belay
authors.forename: Hernan
authors.initials: H
authors.lastname: Aviles
authors.forename: Monique
authors.initials: M
authors.lastname: Vance
authors.forename: Kimberly
authors.initials: K
authors.lastname: Fountain
authors.forename: Gerald
authors.initials: G
authors.lastname: Sonnenfeld
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D006614:Hindlimb; D019417:Hindlimb Suspension / Q000009:adverse effects*; D007113:Immunity, Innate; D007668:Kidney / Q000382:microbiology; D007710:Klebsiella Infections / Q000382:microbiology*; D007711:Klebsiella pneumoniae / Q000254:growth & development*; D008099:Liver / Q000382:microbiology; D008168:Lung / Q000382:microbiology; D051379:Mice; D013026:Space Flight; D013154:Spleen / Q000382:microbiology; D015996:Survival Rate; D013997:Time Factors
keywords: NASA Discipline Regulatory Physiology; Non-NASA Center