Show simple item record

dc.contributor.authorStrick-Marchand, H
dc.contributor.authorDusseaux, M
dc.contributor.authorDarche, S
dc.contributor.authorHuntington, ND
dc.contributor.authorLegrand, N
dc.contributor.authorMasse-Ranson, G
dc.contributor.authorCorcuff, E
dc.contributor.authorAhodantin, J
dc.contributor.authorWeijer, K
dc.contributor.authorSpits, H
dc.contributor.authorKremsdorf, D
dc.contributor.authorDi Santo, JP
dc.date.accessioned2020-12-22T02:41:24Z
dc.date.available2020-12-22T02:41:24Z
dc.date.issued2015-03-17
dc.identifierpii: PONE-D-14-52228
dc.identifier.citationStrick-Marchand, H., Dusseaux, M., Darche, S., Huntington, N. D., Legrand, N., Masse-Ranson, G., Corcuff, E., Ahodantin, J., Weijer, K., Spits, H., Kremsdorf, D. & Di Santo, J. P. (2015). A Novel Mouse Model for Stable Engraftment of a Human Immune System and Human Hepatocytes. PLOS ONE, 10 (3), https://doi.org/10.1371/journal.pone.0119820.
dc.identifier.issn1932-6203
dc.identifier.urihttp://hdl.handle.net/11343/257690
dc.description.abstractHepatic infections by hepatitis B virus (HBV), hepatitis C virus (HCV) and Plasmodium parasites leading to acute or chronic diseases constitute a global health challenge. The species tropism of these hepatotropic pathogens is restricted to chimpanzees and humans, thus model systems to study their pathological mechanisms are severely limited. Although these pathogens infect hepatocytes, disease pathology is intimately related to the degree and quality of the immune response. As a first step to decipher the immune response to infected hepatocytes, we developed an animal model harboring both a human immune system (HIS) and human hepatocytes (HUHEP) in BALB/c Rag2-/- IL-2Rγc-/- NOD.sirpa uPAtg/tg mice. The extent and kinetics of human hepatocyte engraftment were similar between HUHEP and HIS-HUHEP mice. Transplanted human hepatocytes were polarized and mature in vivo, resulting in 20-50% liver chimerism in these models. Human myeloid and lymphoid cell lineages developed at similar frequencies in HIS and HIS-HUHEP mice, and splenic and hepatic compartments were humanized with mature B cells, NK cells and naïve T cells, as well as monocytes and dendritic cells. Taken together, these results demonstrate that HIS-HUHEP mice can be stably (> 5 months) and robustly engrafted with a humanized immune system and chimeric human liver. This novel HIS-HUHEP model provides a platform to investigate human immune responses against hepatotropic pathogens and to test novel drug strategies or vaccine candidates.
dc.languageEnglish
dc.publisherPUBLIC LIBRARY SCIENCE
dc.rights.urihttps://creativecommons.org/licenses/by/4.0
dc.titleA Novel Mouse Model for Stable Engraftment of a Human Immune System and Human Hepatocytes
dc.typeJournal Article
dc.identifier.doi10.1371/journal.pone.0119820
melbourne.affiliation.departmentMedical Biology (W.E.H.I.)
melbourne.source.titlePLoS One
melbourne.source.volume10
melbourne.source.issue3
dc.rights.licenseCC BY
melbourne.elementsid994198
melbourne.contributor.authorHuntington, Nicholas
dc.identifier.eissn1932-6203
melbourne.accessrightsOpen Access


Files in this item

Thumbnail

This item appears in the following Collection(s)

Show simple item record