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Evaluation of Host-Pathogen Interactions during Exposure to Microgravity Analogues (NNJ04HF75G)
Principal Investigator
Research Area:
Species Studied
Scientific Name: Homo sapiens Species: Human Strain: 3-D cell cultures

Changes that occur to both the host immune system and pathogenesis of microbes during space flight could represent a formidable challenge to the successful transition from short-to-long-duration space flight. This is a critical issue to address for several reasons, since a) in-flight infections could potentially pose serious risks to the health, safety, and performance of the flight crew, b) studies have indicated that space flight negatively impacts the immune system in both humans and animals, and c) culture of the ubiquitous human bacterial pathogen, Salmonella typhimurium, under conditions simulating aspects of space flight has been shown to increase the disease causing property of this organism.

Microbiological risks associated with space flight are expected to increase with the length of mission duration. However, the effect(s) of microgravity on the risk of infectious disease events during space flight is not well characterized. In particular, no information is available regarding the ability of microgravity to alter the dynamics of the host-pathogen interaction which leads to infection. Moreover, the biological importance of the immunological changes induced by space flight with regard to resistance to infection remains to be established. A significant application of this research is that by investigating host susceptibility to infection when both the host and pathogen are exposed to microgravity analogues means that mechanistic effects of space flight on host resistance to infection can perhaps be identified.

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Barrila J, Radtke AL, Crabbé A, Sarker SF, Herbst-Kralovetz MM, Ott CM, Nickerson CA. Organotypic 3D cell culture models: using the rotating wall vessel to study host-pathogen interactions. Nat Rev Microbiol. 2010 Nov;8(11):791-801. []

Crabbé A, Sarker SF, Van Houdt R, Ott CM, Leys N, Cornelis P, Nickerson CA. Alveolar epithelium protects macrophages from quorum sensing-induced cytotoxicity in a three-dimensional co-culture model. Cell Microbiol. 2010 Nov 5. []

Crabbé A, Schurr MJ, Monsieurs P, Morici L, Schurr J, Wilson JW, Ott CM, Tsaprailis G, Pierson DL, Stefanyshyn-Piper H, Nickerson CA. Transcriptional and proteomic response of Pseudomonas aeruginosa PAO1 to spaceflight conditions involves Hfq regulation and reveals a role for oxygen. Appl Environ Microbiol. 2010 Dec 17. []

Hjelm BE, Berta AN, Nickerson CA, Arntzen CJ, Herbst-Kralovetz MM. Development and characterization of a three-dimensional organotypic human vaginal epithelial cell model. Biol Reprod. 2010 Mar;82(3):617-27. Epub 2009 Dec 9. []

Nickerson CA, Richter EG, Ott CM. Studying host-pathogen interactions in 3-D: organotypic models for infectious disease and drug development. J Neuroimmune Pharmacol. 2007 Mar;2(1):26-31. Review. Mar-2007. []

Radtke AL, Wilson JW, Sarker S, Nickerson CA. Analysis of interactions of Salmonella type three secretion mutants with 3-D intestinal epithelial cells. PLoS One. 2010 Dec 29;5(12):e15750. []

Skardal A, Sarker SF, Crabbé A, Nickerson CA, Prestwich GD. The generation of 3-D tissue models based on hyaluronan hydrogel-coated microcarriers within a rotating wall vessel bioreactor. Biomaterials. 2010 Nov;31(32):8426-35. Epub 2010 Aug 7.[]

Carterson AJ, Höner zu Bentrup K, Ott CM, Clarke MS, Pierson DL, Vanderburg CR, Buchanan KL, Nickerson CA, Schurr MJ. A549 lung epithelial cells grown as three-dimensional aggregates: alternative tissue culture model for Pseudomonas aeruginosa pathogenesis. Infect Immun. 2005 Feb;73(2):1129-40.

Crabbé A, Pycke B, Van Houdt R, Monsieurs P, Nickerson C, Leys N, Cornelis P. Response of Pseudomonas aeruginosa PAO1 to low shear modelled microgravity involves AlgU regulation. Environ Microbiol. 2010 Jun;12(6):1545-64.

Höner zu Bentrup K, Ramamurthy R, Ott CM, Emami K, Nelman-Gonzalez M, Wilson JW, Richter EG, Goodwin TJ, Alexander JS, Pierson DL, Pellis N, Buchanan KL, Nickerson CA. Three-dimensional organotypic models of human colonic epithelium to study the early stages of enteric salmonellosis. Microbes Infect. 2006 Jun;8(7):1813-25.

LaMarca HL, Ott CM, Höner Zu Bentrup K, Leblanc CL, Pierson DL, Nelson AB, Scandurro AB, Whitley GS, Nickerson CA, Morris CA. Three-dimensional growth of extravillous cytotrophoblasts promotes differentiation and invasion. Placenta. 2005 Nov;26(10):709-20.

Myers TA, Nickerson CA, Kaushal D, Ott CM, Höner zu Bentrup K, Ramamurthy R, Nelman-Gonzalez M, Pierson DL, Philipp MT. Closing the phenotypic gap between transformed neuronal cell lines in culture and untransformed neurons. J Neurosci Methods. 2008 Sep 15;174(1):31-41.

Nickerson CA, Honer zu Bentrup K, Ott CM. Three-dimensional cell culture models for drug discovery and infectious disease. Bioforum Europe. 2005 Nov;6:34-6. , Nov-2005.

Straub TM, Höner zu Bentrup K, Orosz-Coghlan P, Dohnalkova A, Mayer BK, Bartholomew RA, Valdez CO, Bruckner-Lea CJ, Gerba CP, Abbaszadegan M, Nickerson CA. In vitro cell culture infectivity assay for human noroviruses. Emerg Infect Dis. 2007 Mar;13(3):396-403.

Immune system
Host-Pathogen Interactions

Data Information
Data Availability
Archive is complete. No data sets are available for this experiment. Please Contact LSDA if you know of available data for this investigation.

3D aggregates
3D intestinal cells
HT29 monolayers
Innate immune responses
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Mission/Study Information
Mission Launch/Start Date Landing/End Date Duration
Ground 05/01/2009 In Progress

Human Research Program (HRP) Human Research Roadmap (HRR) Information
Crew health and performance is critical to successful human exploration beyond low Earth orbit. The Human Research Program (HRP) investigates and mitigates the highest risks to human health and performance, providing essential countermeasures and technologies for human space exploration. Risks include physiological and performance effects from hazards such as radiation, altered gravity, and hostile environments, as well as unique challenges in medical support, human factors, and behavioral health support. The HRP utilizes an Integrated Research Plan (IRP) to identify the approach and research activities planned to address these risks, which are assigned to specific Elements within the program. The Human Research Roadmap is the web-based tool for communicating the IRP content.

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Additional Information
Managing NASA Center
Johnson Space Center (JSC)
Responsible NASA Representative
Johnson Space Center LSDA Office
Project Manager: Terry Hill
Institutional Support
National Aeronautics and Space Administration (NASA)
Alternate Experiment Name
Proposal Date
Proposal Source