Effects of the hindlimb-unloading model of spaceflight conditions on resistance of mice to infection with Klebsiella pneumoniae.
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.
Belay
Tesfaye
T
Department of Microbiology, Biochemistry, and Immunology, Morehouse School of Medicine, 720 Westview Drive SW, Atlanta, GA 30310-1495.
Aviles
Hernan
H
Vance
Monique
M
Fountain
Kimberly
K
Sonnenfeld
Gerald
G
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
NASA Discipline Regulatory Physiology; Non-NASA Center