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Cited by 43Spaceflight effects on biologyEffects of Radiation ExposureImmunotoxicology and immune responses

Hindlimb suspension and spe-like radiation impairs clearance of bacterial infections

Open access
Li, Minghong, Holmes, Veronica, Zhou, Yu, Ni, Houping, Sanzari, Jenine K., Kennedy, Ann R., Weissman, Drew·2014·PLoS ONE
DOI 10.1371/journal.pone.0085665PMC PMC3893249
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Abstract

A major risk of extended space travel is the combined effects of weightlessness and radiation exposure on the immune system. In this study, we used the hindlimb suspension model of microgravity that includes the other space stressors, situational and confinement stress and alterations in food intake, and solar particle event (SPE)-like radiation to measure the combined effects on the ability to control bacterial infections. A massive increase in morbidity and decrease in the ability to control bacterial growth was observed using 2 different types of bacteria delivered by systemic and pulmonary routes in 3 different strains of mice. These data suggest that an astronaut exposed to a strong SPE during extended space travel is at increased risk for the development of infections that could potentially be severe and interfere with mission success and astronaut health.

AI snapshot

Written from the paper’s full text.

TL;DR

Hindlimb suspension and SPE-like radiation each impaired bacterial clearance in mice, and their combination produced at least additive, often greater-than-additive morbidity. The findings suggest astronauts on extended missions outside Earth’s magnetic field may face increased risk of severe infections.

Key findings

  • Mice given both hindlimb suspension and 2 Gy proton radiation showed a significant inability to clear *Klebsiella pneumoniae* from lungs and blood after inhalation, and *Pseudomonas aeruginosa* from blood after intraperitoneal challenge.
  • Radiation alone increased morbidity; combining radiation with hindlimb suspension had at least an additive effect and often a greater-than-additive effect on morbidity.
  • Gamma and proton radiation produced similar effects, with no significant difference and an RBE of approximately 1; 1.5 Gy gamma was similar to 2 Gy, while 1 Gy gamma gave results similar to hindlimb suspension alone.
  • Hindlimb suspension, with or without radiation, blunted the expected increase in peripheral blood granulocytes after bacterial challenge; total corticosterone increased with suspension and/or radiation and was further elevated with both.

Methods

  • Male and female outbred ICR, Balb/c, and C3H/HeN mice, 5–6 weeks old, were used in groups of 10 per treatment. Mice were whole-body irradiated with 1–2 Gy gamma or proton radiation at 50 cGy/min and/or hindlimb suspended by the tail at 15° head-down tilt.
  • Five days later, mice were challenged with *Pseudomonas aeruginosa* intraperitoneally or *Klebsiella pneumoniae* by inhalation, then followed for 5 days. Blood and lung homogenates were plated for CFU counts, morbidity was scored daily, and blood was analyzed for granulocytes and serum corticosterone.
  • Statistical analyses used 2-way ANOVA for granulocytes and corticosterone, Friedman ANOVA with Wilcoxon signed-rank post-hoc and Bonferroni correction for bacterial counts, and log rank tests on Kaplan-Meier curves for morbidity.

Limitations

  • The paper states that formal RBE calculations were not performed because no significant difference between gamma and proton radiation was evident.
  • The paper states that challenge doses used OD600 as a less accurate surrogate for CFU/µl, which caused differences across experiments in total morbid events or failure to clear bacteremia, although relative increases were consistent.
  • Evident from the text: this is a mouse hindlimb-suspension model, not actual spaceflight, and the mechanisms of the abnormal granulocyte response are not established; the authors note studies are ongoing.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.1371/journal.pone.0085665

Cites

63 of 63 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

0 of 57 cited sources checked · 0 supported · 0 flagged

  • Findingown data

    When expressed as relative increase in morbidity and replicate experiments were analyzed together, hindlimb suspension and radiation led to statistically significant increases in morbidity.

    “When expressed as relative increase in morbidity and replicate experiments were analyzed together, hindlimb suspension and radiation led to statistically significant increases in morbidity.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: The hindlimb suspension model of microgravity includes the other space stressors, situational and confinement stress and alterations in food intake.
  • Findingown data

    The relative increases in morbidity were similar for all 3 strains of mice.

    “The relative increases in morbidity were similar for all 3 strains of mice”
    Quote in the paperSubstantial claim
  • Findingown data

    One Gy of gamma radiation gave similar results as mice treated with hindlimb suspension alone.

    “One Gy of gamma radiation gave similar results as mice treated with hindlimb suspension alone (Figure 5B).”
    Quote in the paperNot a substantial claim
  • Findingown data

    Gamma irradiated mice treated with hindlimb suspension fail to control a challenge with Pseudomonas aeruginosa.

    “Gamma irradiated mice treated with hindlimb suspension fail to control a challenge with Pseudomonas aeruginosa.”
    Quote in the paperSubstantial claim
  • Findingown data

    Hindlimb suspension impairs the increase in peripheral blood granulocytes during systemic bacteremia.

    “Hindlimb suspension impairs the increase in peripheral blood granulocytes during systemic bacteremia.”
    Quote in the paperSubstantial claim
  • May combine two claims. 20
  • Classified as probably not a substantial claim. 19

  • May combine two claims.

    Findingown data

    Two Gy of gamma radiation yielded similar amounts of increased morbidity and an at least additive effect when combined with hindlimb suspension.

    “Two Gy of gamma radiation yielded similar amounts of increased morbidity and an at least additive effect when combined with hindlimb suspension (Figure 5A–B).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Similar data were obtained for males and females and for gamma and proton radiation.

    “Similar data was obtained for males and females and gamma and proton radiation (Figure 5 and 6).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Both hindlimb suspension and SPE-like proton or reference gamma radiation impaired the ability to control and clear infections.

    “Both hindlimb suspension and SPE-like proton or reference gamma radiation impaired the ability to control and clear infections and the combination, as could occur during an extended mission outside the Earth's magnetic field, resulted in at least an additive effect resulting in high levels of morbidity.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: The hindlimb suspension model of microgravity includes the other space stressors, situational and confinement stress and alterations in food intake.

  • May combine two claims.

    Findingown data

    In C3H/HeN mice, radiation alone resulted in a statistically significant increase in morbidity, and the combination of radiation and hindlimb suspension had at least an additive effect on increasing morbidity.

    “Radiation alone resulted in a statistically significant increase in morbidity and the combination of radiation and hindlimb suspension had at least an additive effect on increasing morbidity and often a greater than additive effect (Figure 4).”
    Quote in the paperSubstantial claim
    • Rests on an assumption: The hindlimb suspension model of microgravity includes the other space stressors, situational and confinement stress and alterations in food intake.

  • May combine two claims.

    Findingown data

    The combination of hindlimb suspension and radiation is at least additive and often greater than additive.

    “and the combination is at least additive and often greater than additive.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Hindlimb suspension and/or 2 Gy of proton radiation increases serum total corticosterone levels.

    “Hindlimb suspension and/or 2 Gy of proton radiation increases serum total corticosterone levels.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Either hindlimb suspension or radiation alone results in increased morbidity and reduced ability to clear bacteria.

    “Either hindlimb suspension or radiation alone results in increased morbidity and reduced ability to clear bacteria”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    No significant difference in the effect of gamma versus proton radiation was evident, yielding an RBE of 1.

    “Formal RBE calculations were not performed, as no significant difference in the effect of gamma versus proton radiation was evident, yielding an RBE of 1.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    Space flight alters immune responses, certain of which could lead to potentially detrimental pathology.

    “Space flight has been shown to alter immune responses, certain of which could lead to potentially detrimental pathology.”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [1] R Meehan, 1993, The role of psychoneuroendocrine factors on spaceflight-induced immunological alterations, J Leukoc Biol source

      Not checked in the free run.

    • cites [2] KX Wang, 2007, Osteopontin regulates hindlimb-unloading-induced lymphoid organ atrophy and weight loss by modulating corticosteroid production, Proc Natl Acad Sci U S A source

      Not checked in the free run.

    • cites [3] VM Aponte, 2006, Considerations for non-invasive in-flight monitoring of astronaut immune status with potential use of MEMS and NEMS devices, Life Sci source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Solar particle events (SPEs) can result in sufficiently high radiation doses to cause the symptoms of acute radiation sickness (ARS) in astronauts outside the protection of Earth's geomagnetic field, as well as threaten mission success.

    “Occasional periods of high energy particle flux from the sun, known as SPEs, can result in sufficiently high radiation doses to cause the symptoms of acute radiation sickness (ARS) in astronauts outside the protection of Earth's geomagnetic field, as well as threaten mission success [27].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [27] S Hu, 2009, Modeling the acute health effects of astronauts from exposure to large solar particle events, Health Phys source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    The challenge inoculum was spread on agar plates to confirm the challenge dose.

    “The challenge inoculum was spread on agar plates to confirm the challenge dose.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Exposure to SPE radiation results in an inhomogeneous dose distribution, with high skin doses and lower internal organ doses, since the majority of the protons in SPEs have kinetic energies of 100 MeV or less, which have limited penetrating abilities.

    “Exposure to SPE radiation results in an inhomogeneous dose distribution, with high skin doses and lower internal organ doses, since the majority of the protons in SPEs have kinetic energies of 100 MeV or less, which have limited penetrating abilities [28].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [28] W Clegg, 2013, Structural elucidation of homometallic anthracenolates synthesised via deprotonative metallation of anthrone, Dalton Trans source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Space travel is associated with decreases, sometimes severe, in cell-mediated immunity with altered cytokine production.

    “The consistent effects on the immune system observed during space travel, thus far, are a reduction in peripheral T-cell counts; a decrease in NK cell number and functionality [12], [13]; decreases, sometimes severe, in cell-mediated immunity with altered cytokine production [13], [14]; and normal levels of serum immunoglobulins [13].”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [13] DS Levine, 1998, Immunosuppression during spaceflight deconditioning, Aviat Space Environ Med

      Not checked in the free run.

    • cites [14] BE Crucian, 2000, Altered cytokine production by specific human peripheral blood cell subsets immediately following space flight, J Interferon Cytokine Res source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    SPEs consist primarily of relatively low energy protons, with a minor contribution of electrons, alpha particles and heavier particles of high charge and energy (HZE particles).

    “SPEs consist primarily of relatively low energy protons, with a minor contribution of electrons, alpha particles and heavier particles of high charge and energy, known as HZE particles [28].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [28] W Clegg, 2013, Structural elucidation of homometallic anthracenolates synthesised via deprotonative metallation of anthrone, Dalton Trans source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    SPEs occur quite often (with frequencies of up to 3 per day), but it is difficult to predict their onset and size; the expected overall frequency is strongly influenced by the solar cycle, with a general increase in SPE occurrence with increasing solar activity.

    “SPEs occur quite often (with frequencies of up to 3 per day [29]), but it is difficult to predict their onset and size; the expected overall frequency, however, is strongly influenced by the solar cycle, with a general increase in SPE occurrence with increasing solar activity [29].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [29] MH Kim, 2009, Prediction of frequency and exposure level of solar particle events, Health Phys source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    SPEs can last from several hours to several weeks.

    “SPEs can last from several hours to several weeks [29], [30], [31].”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [29] MH Kim, 2009, Prediction of frequency and exposure level of solar particle events, Health Phys source

      Not checked in the free run.

    • cites [30] L Hu, 2009, Selective on-line serum peptide extraction and multidimensional separation by coupling a restricted-access material-based capillary trap column with nanoliquid chromatography-tandem mass spectrometry, J Chromatogr A source

      Not checked in the free run.

    • cites [31] SE Baillie, 2012, New lithium-zincate approaches for the selective functionalisation of pyrazine: direct dideprotozincation vs. nucleophilic alkylation, Chem Commun source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Space travel is associated with normal levels of serum immunoglobulins.

    “The consistent effects on the immune system observed during space travel, thus far, are a reduction in peripheral T-cell counts; a decrease in NK cell number and functionality [12], [13]; decreases, sometimes severe, in cell-mediated immunity with altered cytokine production [13], [14]; and normal levels of serum immunoglobulins [13].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [13] DS Levine, 1998, Immunosuppression during spaceflight deconditioning, Aviat Space Environ Med

      Not checked in the free run.

  • Classified as probably not a substantial claim. May combine two claims.

    Premisecitation

    Cortisol or corticosterone is induced during various types of stress and impairs both innate and acquired immune function.

    “Cortisol or corticosterone is induced during various types of stress and impairs both innate and acquired immune function (reviewed in [51]).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [51] DA Padgett, 2003, How stress influences the immune response, Trends Immunol source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductreasoning

    All samples from each experiment were analyzed at the same time to avoid possible variations in flow rates that could occur at different days, temperatures, or relative humidities.

    “All samples from each experiment were analyzed at the same time to avoid possible variations in flow rates that could occur at different days, temperatures, or relative humidities.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Differences in immune reactivity and susceptibility to infectious diseases between males and females are well described.

    “Differences in immune reactivity and susceptibility to infectious diseases between males and females is well described (reviewed in [40], [41], [46], [47], [48]).”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [40] JC Fischer, 2011, Reducing costs in flow-cytometric counting of residual white blood cells in blood products: utilization of a single-platform bead-free flow-rate calibration method, Transfusion source

      Not checked in the free run.

    • cites [41] Walker C, Barnett D (2006) Flow rate calibration for absolute cell counting rationale and design. Current protocols in cytometry/editorial board, J Paul Robinson Chapter 6: Unit 6 24. source

      Not checked in the free run.

    • cites [46] B Crucian, 2009, Immune system dysregulation during spaceflight: clinical risk for exploration-class missions, J Leukocyte Biol source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Balb/c mice are considered a radiation sensitive strain and are used as a representative surrogate for humans with similar increased sensitivity to radiation effects due to reduced repair enzyme function.

    “Balb/c mice are considered a radiation sensitive strain and are used as a representative surrogate for humans with similar increased sensitivity to radiation effects due to reduced repair enzyme function [45].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [45] YP Fu, 2003, Breast cancer risk associated with genotypic polymorphism of the nonhomologous end-joining genes: a multigenic study on cancer susceptibility, Cancer Res

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    It has been estimated that the highest dose to internal organs from exposure to SPE radiation would be 2 Gy.

    “It has been estimated that the highest dose to internal organs from exposure to SPE radiation would be 2 Gy [34].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [34] LW Townsend, 2005, Implications of the space radiation environment for human exploration in deep space, Radiat Prot Dosimetry source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    The protocol was approved by the Institutional Animal Care and Use Committee (Assurance # A3079-01) of the University of Pennsylvania.

    “The protocol was approved by the Institutional Animal Care and Use Committee (Assurance # A3079-01) of the University of Pennsylvania.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Space travel is associated with a decrease in NK cell number and functionality.

    “The consistent effects on the immune system observed during space travel, thus far, are a reduction in peripheral T-cell counts; a decrease in NK cell number and functionality [12], [13]; decreases, sometimes severe, in cell-mediated immunity with altered cytokine production [13], [14]; and normal levels of serum immunoglobulins [13].”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [12] G Sonnenfeld, 2002, Immune function during space flight, Nutrition source

      Not checked in the free run.

    • cites [13] DS Levine, 1998, Immunosuppression during spaceflight deconditioning, Aviat Space Environ Med

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Study design and conductown data

    The maximal number of CFUs of each bacterium in each mouse strain that an untreated control mouse could control with minimal morbidity was calculated.

    “The maximal number of CFUs of each bacterium in each mouse strain that an untreated control mouse could control with minimal morbidity was calculated.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: The hindlimb suspension model of microgravity includes the other space stressors, situational and confinement stress and alterations in food intake.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Using the historical August 1972 SPE, the estimated doses that an astronaut could receive would be 3215 cGy to the skin and 138.4 cGy-equivalent (cGy-eq) to the blood forming organs during EVA.

    “Using the historical August 1972 SPE, the estimated doses that an astronaut could receive would be 3215 cGy to the skin and 138.4 cGy-equivalent (cGy-eq) to the blood forming organs during EVA [27].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [27] S Hu, 2009, Modeling the acute health effects of astronauts from exposure to large solar particle events, Health Phys source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    Dosimetry verification was performed before the irradiations with a 2D ion chamber array.

    “Dosimetry verification was performed before the irradiations with a 2D ion chamber array (I'mRT MatriXX, IBA dosimetry) placed at a depth of 13.3 cm WET.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    All mice, including controls, were placed in irradiation chambers for the same amount of time.

    “All mice, including controls, were placed in irradiation chambers for the same amount of time.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Suspended mice given subcutaneous Pseudomonas aeruginosa had increased mortality and organ bacterial load and an increase in corticosterone.

    “Suspended mice given subcutaneous Pseudomonas aeruginosa had increased mortality and organ bacterial load and an increase in corticosterone [25].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [25] H Aviles, 2003, Increased susceptibility to Pseudomonas aeruginosa infection under hindlimb-unloading conditions, J Appl Physiol source

      Not checked in the free run.

  • May combine two claims.

    Interpretationown data

    Our data agree with and extend previous data to include the additional space risk of SPE-like radiation.

    “Our data agree with and extends these data to include the additional space risk of SPE-like radiation.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Previous studies have observed a range of immune defects induced by the hindlimb suspension model of microgravity.

    “Previous studies have observed a range of immune defects induced by the hindlimb suspension model of microgravity”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [54] JM Steffen, 1986, Thymic involution in the suspended rat: adrenal hypertrophy and glucocorticoid receptor content, Aviat Space Environ Med

      Not checked in the free run.

    • cites [55] SD Fleming, 1990, Test of the antiorthostatic suspension model on mice: effects on the inflammatory cell response, Aviat Space Environ Med

      Not checked in the free run.

    • cites [23] EH Lee, 2005, Tumor growth and immune function in mice during hind-limb unloading, Aviat Space Environ Med

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Studies of humans receiving cancer chemotherapy have indicated that the risk of infection increases as the peripheral granulocyte count decreases.

    “Studies of humans receiving cancer chemotherapy have indicated that the risk of infection increases as the peripheral granulocyte count decreases”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [53] CR Flowers, 2013, Antimicrobial prophylaxis and outpatient management of fever and neutropenia in adults treated for malignancy: American Society of Clinical Oncology clinical practice guideline, J Clin Oncol source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    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].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [24] T Belay, 2002, Effects of the hindlimb-unloading model of spaceflight conditions on resistance of mice to infection with Klebsiella pneumoniae, J Allergy Clin Immunol source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S4 (based).

    Study design and conductnone given

    We used doses of bacteria that control mice could consistently control.

    “We used doses of bacteria that control mice could consistently control”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    SPEs are unpredictable and an astronaut is expected to have less than one hour notice, or no notice at all, of an incoming SPE.

    “they are unpredictable and it is expected that an astronaut will have less than one hour notice, or no notice at all, of an incoming SPE [52].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [52] Townsend LW, Badhwar GD, Braby LA, Blakely EA, Cucinotta FA, et al. (2006) Information Needed to Make Radiation Protection Recommendations for Space Missions Beyond Low-Earth Orbit. Bethesda.

      Not checked in the free run.

35 of 35

  • The paper relies on this without support.

    During travel outside the Earth's magnetic field, an astronaut would be subjected to variable and extended durations of time in microgravity before exposure to a potentially harmful SPE.

    “During travel outside the Earth's magnetic field, an astronaut would be subjected to variable and extended durations of time in microgravity before exposure to a potentially harmful SPE.”

  • The paper relies on this without support.

    C3H/HeN mice have no known defects or polymorphisms that impair DNA repair or the response to ionizing radiation.

    “C3H/HeN mice are inbred and have no known defects or polymorphisms that impair DNA repair or the response to ionizing radiation.”

  • The paper relies on this without support.

    The hindlimb suspension model of microgravity includes the other space stressors, situational and confinement stress and alterations in food intake.

    “In this study, we used the hindlimb suspension model of microgravity that includes the other space stressors, situational and confinement stress and alterations in food intake, and solar particle event (SPE)-like radiation to measure the combined effects on the ability to control bacterial infections.”

  • The paper relies on this without support.

    Hindlimb suspension is a valid model of microgravity for studying immune effects on bacterial infection.

    “We used the hindlimb unloading model of microgravity and proton radiation with an energy spectrum similar to that expected during an SPE, as well as reference gamma radiation, to determine the effect of these space conditions on controlling bacterial infection.”

  • The paper relies on this without support.

    The immune response of mice to hindlimb suspension and radiation is representative of that of astronauts during spaceflight.

    “any increase in morbidity or decrease in clearance of bacteria is directly applicable to astronaut exposures during space flight.”

  • The paper relies on this without support.

    Stress is a major physiological strain during spaceflight that is modeled during hindlimb suspension.

    “A major physiological strain during spaceflight that is modeled during hindlimb suspension is stress that can negatively regulate immune function.”

  • The paper relies on this without support.

    Pseudomonas aeruginosa and Klebsiella pneumoniae have been demonstrated to cause infections in astronauts during spaceflight.

    “using 2 different bacteria previously demonstrated to cause infections in astronauts during spaceflight”
7 of 7

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • In a mouse model, T-cells did not become activated following exposure to low doses of SPE-like proton radiation, and the animals were susceptible to a non-toxic bacterial challenge of organisms (Pseudomonas aeruginosa, Klebsiella pneumoniae) that are relatively innocuous and ubiquitous on Earth and have been detected aboard the ISS.

    “In a mouse model, T-cells did not become activated following exposure to low doses of SPE-like proton radiation, and the animals were susceptible to a non-toxic bacterial challenge of organisms (Pseudomonas aeruginosa, Klebsiella pneumoniae) that are relatively innocuous and ubiquitous on Earth and have been detected aboard the ISS [65,66].”

    From Space Radiation: The number one risk to astronaut health beyond low earth orbit (2014) · cites this paper as [66]

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

Each contradiction between two passages listed here was confirmed by an independent check.

  • Figure 4 is cited for ICR mice but depicts C3H/HeN mice

    Minor

    The Results cite Figure 4 as evidence for ICR mice, but its caption identifies the mice as C3H/HeN.

  • Free corticosterone reported, but only total corticosterone was measured

    Minor

    The Results describe a further elevation in free corticosterone in the combined-treatment group, while the Figure 9 caption identifies the measurement as total corticosterone. The text does not report a separate free-corticosterone measurement.

2 of 2

Cites

Flagged first, then by citations

Research works printed but not linked: 2

  1. B Crucian, 2009, Immune system dysregulation during spaceflight: clinical risk for exploration-class missions, J Leukocyte Biol, 86, 1017, 10.1189/jlb.0709500 · DOI · Paper page
  2. LA Mermel, 2013, Infection prevention and control during prolonged human space travel, Clinical Infect Dis, 56, 123, 10.1093/cid/cis861 · DOI

Cited by

Sorted by citations

Related

Authors
Li, M., Holmes, V., Zhou, Y., Ni, H., Sanzari, J. K., Kennedy, A. R., & Weissman, D.
Affiliations
University of Pennsylvania (US)
Corresponding author
Weissman, Drew
ORCID
Venue
PLoS ONE
Publisher
Public Library of Science (PLoS)
Published
2014-01-15
Volume
9
Issue
1
Pages
e85665
ISSN
1932-6203 (ISSN-L)
DOI
10.1371/journal.pone.0085665
PMC
PMC3893249
OpenAlex
W2073616573
Cited by
43
References
63
Citations by year
2026: 2 · 2025: 2 · 2024: 1 · 2023: 2 · 2022: 3 · 2021: 4 · 2020: 5 · 2019: 5 · 2018: 5 · 2017: 1 · 2016: 3 · 2015: 5 · 2014: 4 · 2013: 1
FWCI
2.88
Type
journal article
Language
en
Open access
Licence
Locations
  • PLoS ONE (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • National Aeronautics and Space Administration (NASA NCC 9‐58, NCC958)
  • National Space Biomedical Research Institute (NASA NCC 9‐58, NCC 9‐58)
Topics
  • Health Sciences › Medicine › Physiology › Spaceflight effects on biology
  • Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Effects of Radiation Exposure
  • Life Sciences › Immunology and Microbiology › Immunology › Immunotoxicology and immune responses
Keywords
hindlimb unloading, microgravity, astronaut health, spaceflight immunology, situational stress, confinement stress, dietary intake, pulmonary infection, systemic infection, mouse model
MeSH terms
Animals, Corticosterone, Female, Humans, Immunity, Innate, Klebsiella Infections, Male, Mice, Inbred BALB C, Mice, Inbred C3H, Mice, Inbred ICR, Peritonitis, Pseudomonas Infections, Radiation Injuries, Experimental, Respiratory Tract Infections, Space Flight, Stress, Psychological, Bacteremia, Hindlimb Suspension, Solar Activity, Mice

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-10.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-10.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

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