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.Conclusion 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.
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Animal models of space flight have demonstrated a reduced ability to clear infections by Klebsiella pneumoniae and Pseudomonas aeruginosa.
“Animal models of space flight have demonstrated a reduced ability to clear infections by Klebsiella pneumoniae [24] and Pseudomonas aeruginosa [25].”
From Hindlimb suspension and spe-like radiation impairs clearance of bacterial infections (2014) · cites this paper as [24]
Hindlimb suspended mice given IP Klebsiella pneumoniae had an increase in mortality and bacterial organ loads.
“Hindlimb suspended mice given IP Klebsiella pneumoniae similarly had an increase in mortality and bacterial organ loads [24].”
From Hindlimb suspension and spe-like radiation impairs clearance of bacterial infections (2014) · cites this paper as [24]
Studies have indicated a reduction in the ability of hindlimb unloaded mice to control bacterial infections.
“Studies have indicated a reduction in the ability of hindlimb unloaded mice to control bacterial infections.”
From Hindlimb suspension and spe-like radiation impairs clearance of bacterial infections (2014) · cites this paper as [24]
The studies of systemic Klebsiella pneumoniae and Pseudomonas aeruginosa gave mice an LD50 of bacteria, which allowed small changes in immune function to result in significant increases in mortality above the expected 50%.
“The studies of systemic Klebsiella pneumoniae and Pseudomonas aeruginosa gave mice an LD50 of bacteria [24], [25], which allowed small changes in immune function to result in significant increases in mortality above the expected 50%.”
From Hindlimb suspension and spe-like radiation impairs clearance of bacterial infections (2014) · cites this paper as [24]
Cites
A SIMPLE METHOD OF ESTIMATING FIFTY PER CENT ENDPOINTS12
REED, L. J., & Muench, H. (1938) · American Journal of Epidemiology · doi:10.1093/oxfordjournals.aje.a118408 · Cited by 20,341 · see citing works
A simple method of estimating 50 per cent end points
Muench, H. (1938) · Medical Entomology and Zoology · Cited by 8,377 · see citing works
MIF regulates innate immune responses through modulation of Toll-like receptor 4
Roger, T., David, J. R., Glauser, M. P., & Calandra, T. (2001) · Nature · doi:10.1038/414920a · Cited by 584 · see citing works
Bactericidal and bacteriolytic activity of serum against gram-negative bacteria
Taylor, P. W. (1983) · Microbiological Reviews · doi:10.1128/mr.47.1.46-83.1983 · Cited by 440 · see citing works
Catecholamine induced growth of gram negative bacteria
Lyte, M., & Ernst, S. (1992) · Life Sciences · doi:10.1016/0024-3205(92)90273-r · Cited by 396 · see citing works
Spaceflight and Bone Turnover: Correlation with a New Rat Model of Weightlessness
Morey, E. R. (1979) · BioScience · doi:10.2307/1307797 · Cited by 315 · see citing works
Nickerson, C. A., Ott, C. M., Mister, S. J., Morrow, B. J., Burns-Keliher, L., & Pierson, D. L. (2000) · Infection and Immunity · doi:10.1128/iai.68.6.3147-3152.2000 · Cited by 249 · see citing works
Greenberger, M. J., Strieter, R. M., Kunkel, S. L., Danforth, J. M., Laichalk, L. L., McGillicuddy, D. C., & Standiford, T. J. (1996) · The Journal of Infectious Diseases · doi:10.1093/infdis/173.1.159 · Cited by 245 · see citing works
Psychoneuroimmunology: Interactions between central nervous system and immune system
Solomon, G. F. (1987) · Journal of Neuroscience Research · doi:10.1002/jnr.490180103 · Cited by 216 · see citing works
Bactericidal and bacteriolytic activity of serum against gram-negative bacteria.
Taylor, P. W. (1983) · Microbiological Reviews · doi:10.1128/mmbr.47.1.46-83.1983 · Cited by 178 · see citing works
Neuroendocrine–Bacterial Interactions in a Neurotoxin-Induced Model of Trauma
Lyte, M., & Bailey, M. T. (1997) · Journal of Surgical Research · doi:10.1006/jsre.1997.5130 · Cited by 168 · see citing works
The role of microbial endocrinology in infectious disease
Lyte, M. (1993) · Journal of Endocrinology · doi:10.1677/joe.0.1370343 · Cited by 168 · see citing works
Immune changes during long-duration missions
Konstantinova, I., Петровна, Р. М., Lesnyak, A. T., & Antropova, E. A. (1993) · Journal of Leukocyte Biology · doi:10.1002/jlb.54.3.189 · Cited by 160 · see citing works
Stress‐Induced Neuroendocrine Modulation of Viral Pathogenesis and Immunitya
Sheridan, J. F., Dobbs, C. M., Jung, J., Chu, X., Konstantinos, A. P., Padgett, D. A., & Glaser, R. (1998) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.1998.tb09618.x · Cited by 147 · see citing works
Immunological analyses of U.S. Space Shuttle crewmembers.
TAYLOR, G. R., Neale, L. S., & Dardano, J. R. (1986) · PubMed · Cited by 144 · see citing works
(1998) · CRC Press eBooks · doi:10.1201/9781420048193 · Cited by 132 · see citing works
Gregory, S., Cousens, L., van Rooijen, N., Döpp, E., Carlos, T., & Wing, E. (2002) · Journal of Immunology · doi:10.4049/jimmunol.168.1.308 · Cited by 126 · see citing works
Stress and Pathogenesis of Infectious Disease
Peterson, P. K., Chao, C., Molitor, T. W., Murtaugh, M. P., Strgar, F., & Sharp, B. M. (1991) · Clinical Infectious Diseases · doi:10.1093/clinids/13.4.710 · Cited by 105 · see citing works
Neal, C. P., Freestone, P. P. E., Maggs, A. F., Haigh, R., WILLIAMS, P. H., & Lyte, M. (2001) · FEMS Microbiology Letters · doi:10.1111/j.1574-6968.2001.tb09463.x · Cited by 100 · see citing works
Spaceflight alters immune cell function and distribution
Sonnenfeld, G., Mandel, A. D., Konstantinova, I., Berry, W. D., TAYLOR, G. R., Lesnyak, A. T., Fuchs, B. B., & Rakhmilevich, A. L. (1992) · Journal of Applied Physiology · doi:10.1152/jappl.1992.73.2.s191 · Cited by 89 · see citing works
Self-citationEffects of Gravity on Gastric Emptying, Intestinal Transit, and Drug Absorption
Amidon, G. L., DeBrincat, G. A., & Najib, N. M. (1991) · The Journal of Clinical Pharmacology · doi:10.1002/j.1552-4604.1991.tb03658.x · Cited by 85 · see citing works
Differential effects of catecholamines on in vitro growth of pathogenic bacteria
Belay, T., & Sonnenfeld, G. (2002) · Life Sciences · doi:10.1016/s0024-3205(02)01683-1 · Cited by 78 · see citing works
Self-citationAntiorthostatic suspension as a model for the effects of spaceflight on the immune system
Chapes, S. K., Mastro, A. M., Sonnenfeld, G., & Berry, W. D. (1993) · Journal of Leukocyte Biology · doi:10.1002/jlb.54.3.227 · Cited by 75 · see citing works
Self-citationEffects of spaceflight on levels and activity of immune cells.
Sonnenfeld, G., Mandel, A. D., Konstantinova, I., TAYLOR, G. R., Berry, W. D., Wellhausen, S. R., Lesnyak, A. T., & Fuchs, B. B. (1990) · PubMed · Cited by 66 · see citing works
Self-citationCatecholamine enhancement ofAeromonas hydrophilagrowth
Kinney, K. S., Austin, C. E., Morton, D. S., & Sonnenfeld, G. (1999) · Microbial Pathogenesis · doi:10.1006/mpat.1998.0251 · Cited by 64 · see citing works
Self-citationEffect of a 22-day space flight on the lymphoid organs of rats.
Gn, D., Kaplansky, A. S., & Vv, P. (1976) · PubMed · Cited by 53 · see citing works
O’Brien, A., Standiford, T. J., Bucknell, K. A., Wilcoxen, S. E., & Paine, R. (1999) · American Journal of Physiology-Lung Cellular and Molecular Physiology · doi:10.1152/ajplung.1999.276.6.l961 · Cited by 42 · see citing works
Effect of space flight on cell-mediated immunity.
Mandel, A. D., & Balish, E. (1977) · PubMed · Cited by 37 · see citing works
Influence of antiorthostatic suspension on resistance to murine Listeria monocytogenes infection
Miller, E. S., & Sonnenfeld, G. (1994) · Journal of Leukocyte Biology · doi:10.1002/jlb.55.3.371 · Cited by 37 · see citing works
Self-citationA suspension model for hypokinetic/hypodynamic and antiorthostatic responses in the mouse.
Steffen, J. M., Robb, R., Dombrowski, M. J., Musacchia, X. J., Mandel, A. D., & Sonnenfeld, G. (1984) · PubMed · Cited by 34 · see citing works
Self-citationEffects of microgravity on bone and calcium homeostasis
Zérath, E. (1998) · Advances in Space Research · doi:10.1016/s0273-1177(98)00026-x · Cited by 34 · see citing works
Effects of antiorthostatic suspension and corticosterone on macrophage and spleen cell function
Kopydlowski, K. M., McVey, D. S., Woods, K. M., Landolo, J. J., & Chapes, S. K. (1992) · Journal of Leukocyte Biology · doi:10.1002/jlb.52.2.202 · Cited by 34 · see citing works
Gould, C. L., & Sonnenfeld, G. (1988) · PubMed · Cited by 29 · see citing works
Self-citationEffect of a Simulated Weightlessness Model on the Production of Rat Interferon
Sonnenfeld, G., Morey, E. R., Williams, J. A., & Mandel, A. D. (1982) · Journal of Interferon Research · doi:10.1089/jir.1982.2.467 · Cited by 29 · see citing works
Self-citationAvilés, H., & Monroy, F. P. (2001) · NeuroImmunoModulation · doi:10.1159/000049002 · Cited by 22 · see citing works
van Enckevort, F. H. J., Sweep, F. C. G. J., Span, P. N., Netea, M. G., Hermus, A. R. M. M., & Kullberg, B. J. (2001) · PubMed · Cited by 21 · see citing works
Antipyrine pharmacokinetics in the tail-suspended rat model.
Brunner, L. J., DiPiro, J. T., & Feldman, S. L. (1995) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(25)10608-3 · Cited by 14 · see citing works
Antiorthostatic Suspension Stimulates Profiles of Macrophage Activation in Mice
Miller, E. S., Bates, R. A., Koebel, D. A., et al. (1999) · NeuroImmunoModulation · doi:10.1159/000026377 · Cited by 14 · see citing works
Weizman, R., & Bessler, H. (1998) · CRC Press eBooks · doi:10.1201/9781420048193.ch1 · Cited by 10 · see citing works
Steffen, J. M., & Musacchia, X. J. (1984) · PubMed · Cited by 4 · see citing works
Enckevort, F. H. J. V., Sweep, C. G. J., Span, P. N., et al. (2001) · Radboud Repository (Radboud University) · Cited by 2 · see citing works
Infection Associated with the Surgical Care of the Major Trauma Victim
Polk, H. C., Cheadle, W. G., Sonnenfeld, G., et al. (2020) · CRC Press eBooks · doi:10.1201/9781003066903-3 · Cited by 1 · see citing works
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O'Donnell, P. M., Aviles, H., Lyte, M., & Sonnenfeld, G. (2006) · Applied and Environmental Microbiology · doi:10.1128/aem.00075-06 · Cited by 99 · see citing works
Self-citationAviles, H., Belay, T., Fountain, K., Vance, M., Sun, B., & Sonnenfeld, G. (2003) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00259.2003 · Cited by 59 · see citing works
Aviles, H., Belay, T., Fountain, K., Vance, M., & Sonnenfeld, G. (2003) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00968.2002 · Cited by 53 · see citing works
Self-citationSanzari, J. K., Romero-Weaver, A. L., James, G., Krigsfeld, G., Lin, L., Diffenderfer, E. S., & Kennedy, A. R. (2013) · PLoS ONE · doi:10.1371/journal.pone.0071757 · Cited by 47 · see citing works
Hindlimb suspension and spe-like radiation impairs clearance of bacterial infections
Li, M., Holmes, V., Zhou, Y., Ni, H., Sanzari, J. K., Kennedy, A. R., & Weissman, D. (2014) · PLoS ONE · doi:10.1371/journal.pone.0085665 · Cited by 43 · see citing works
- Authors
- Belay, T., Aviles, H., Vance, M., Fountain, K., & Sonnenfeld, G.
- Affiliations
- Morehouse School of Medicine (US)
- ORCID
- Belay, Tesfaye
- Venue
- Journal of Allergy and Clinical Immunology
- Publisher
- Elsevier BV
- Published
- 2002-08
- Volume
- 110
- Issue
- 2
- Pages
- 262-268
- ISSN
- 0091-6749 (ISSN-L)
- OpenAlex
- W1970221893
- Cited by
- 54
- References
- 42
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 1 · 2022: 1 · 2021: 2 · 2020: 3 · 2019: 3 · 2018: 2 · 2017: 1 · 2016: 2 · 2015: 3 · 2014: 4 · 2013: 3 · 2012: 2
- FWCI
- 2.40
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Allergy and Clinical Immunology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Center for Research Resources (5G12 RR/AI 03034)
- Topics
- Health Sciences › Medicine › Physiology › Spaceflight effects on biology
- Health Sciences › Medicine › Epidemiology › Sepsis Diagnosis and Treatment
- Health Sciences › Medicine › Surgery › Cardiovascular Syncope and Autonomic Disorders
- Keywords
- hindlimb unloading, Klebsiella pneumoniae, infection susceptibility, spaceflight immunology, bacterial dissemination, bacterial clearance, mortality, stress, mice
- MeSH terms
- Animals, Disease Models, Animal, Female, Hindlimb, Immunity, Innate, Kidney, Klebsiella Infections, Klebsiella pneumoniae, Liver, Lung, Space Flight, Spleen, Time Factors, Survival Rate, Hindlimb Suspension, Mice
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