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dc.contributor.authorHojo-Souza, Natalia Satchiko
dc.contributor.authorde Azevedo, Patrick Orestes
dc.contributor.authorde Castro, Julia Teixeira
dc.contributor.authorTeixeira-Carvalho, Andrea
dc.contributor.authorLieberman, Judy
dc.contributor.authorJunqueira, Caroline
dc.contributor.authorGazzinelli, Ricardo T.
dc.date2022-08-11T08:09:57.000
dc.date.accessioned2022-08-23T16:50:03Z
dc.date.available2022-08-23T16:50:03Z
dc.date.issued2020-09-10
dc.date.submitted2020-11-02
dc.identifier.citation<p>Hojo-Souza NS, de Azevedo PO, de Castro JT, Teixeira-Carvalho A, Lieberman J, Junqueira C, Gazzinelli RT. Contributions of IFN-γ and granulysin to the clearance of Plasmodium yoelii blood stage. PLoS Pathog. 2020 Sep 10;16(9):e1008840. doi: 10.1371/journal.ppat.1008840. PMID: 32913355; PMCID: PMC7482970. <a href="https://doi.org/10.1371/journal.ppat.1008840">Link to article on publisher's site</a></p>
dc.identifier.issn1553-7366 (Linking)
dc.identifier.doi10.1371/journal.ppat.1008840
dc.identifier.pmid32913355
dc.identifier.urihttp://hdl.handle.net/20.500.14038/41585
dc.description.abstractP. vivax-infected Retics (iRetics) express human leukocyte antigen class I (HLA-I), are recognized by CD8+ T cells and killed by granulysin (GNLY) and granzymes. However, how Plasmodium infection induces MHC-I expression on Retics is unknown. In addition, whether GNLY helps control Plasmodium infection in vivo has not been studied. Here, we examine these questions using rodent infection with the P. yoelii 17XNL strain, which has tropism for Retics. Infection with P. yoelii caused extramedullary erythropoiesis, reticulocytosis and expansion of CD8+CD44+CD62L- IFN-gamma-producing T cells that form immune synapses with iRetics. We now provide evidence that MHC-I expression by iRetic is dependent on IFN-gamma-induced transcription of IRF-1, MHC-I and beta2-microglobulin (beta2-m) in erythroblasts. Consistently, CTLs from infected wild type (WT) mice formed immune synapses with iRetics in an IFN-gamma- and MHC-I-dependent manner. When challenged with P. yoelii 17XNL, WT mice cleared parasitemia and survived, while IFN-gamma KO mice remained parasitemic and all died. beta2-m KO mice that do not express MHC-I and have virtually no CD8+ T cells had prolonged parasitemia, and 80% survived. Because mice do not express GNLY, GNLY-transgenic mice can be used to assess the in vivo importance of GNLY. Parasite clearance was accelerated in GNLY-transgenic mice and depletion of CD8+ T cells ablated the GNLY-mediated resistance to P. yoelii. Altogether, our results indicate that in addition to previously described mechanisms, IFN-gamma promotes host resistance to the Retic-tropic P. yoelii 17XNL strain by promoting MHC-I expression on iRetics that become targets for CD8+ cytotoxic T lymphocytes and GNLY.
dc.language.isoen_US
dc.relation<p><a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=32913355&dopt=Abstract">Link to Article in PubMed</a></p>
dc.rightsCopyright © 2020 Hojo-Souza et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subjectT cells
dc.subjectCytotoxic T cells
dc.subjectPlasmodium yoelii
dc.subjectErythroblasts
dc.subjectParasitic diseases
dc.subjectParasitemia
dc.subjectSpleen
dc.subjectBlood
dc.subjectAmino Acids, Peptides, and Proteins
dc.subjectEnzymes and Coenzymes
dc.subjectHemic and Immune Systems
dc.subjectImmunology of Infectious Disease
dc.subjectParasitic Diseases
dc.subjectParasitology
dc.subjectPathogenic Microbiology
dc.titleContributions of IFN-gamma and granulysin to the clearance of Plasmodium yoelii blood stage
dc.typeJournal Article
dc.source.journaltitlePLoS pathogens
dc.source.volume16
dc.source.issue9
dc.identifier.legacyfulltexthttps://escholarship.umassmed.edu/cgi/viewcontent.cgi?article=5403&amp;context=oapubs&amp;unstamped=1
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/oapubs/4374
dc.identifier.contextkey20053062
refterms.dateFOA2022-08-23T16:50:03Z
html.description.abstract<p>P. vivax-infected Retics (iRetics) express human leukocyte antigen class I (HLA-I), are recognized by CD8+ T cells and killed by granulysin (GNLY) and granzymes. However, how Plasmodium infection induces MHC-I expression on Retics is unknown. In addition, whether GNLY helps control Plasmodium infection in vivo has not been studied. Here, we examine these questions using rodent infection with the P. yoelii 17XNL strain, which has tropism for Retics. Infection with P. yoelii caused extramedullary erythropoiesis, reticulocytosis and expansion of CD8+CD44+CD62L- IFN-gamma-producing T cells that form immune synapses with iRetics. We now provide evidence that MHC-I expression by iRetic is dependent on IFN-gamma-induced transcription of IRF-1, MHC-I and beta2-microglobulin (beta2-m) in erythroblasts. Consistently, CTLs from infected wild type (WT) mice formed immune synapses with iRetics in an IFN-gamma- and MHC-I-dependent manner. When challenged with P. yoelii 17XNL, WT mice cleared parasitemia and survived, while IFN-gamma KO mice remained parasitemic and all died. beta2-m KO mice that do not express MHC-I and have virtually no CD8+ T cells had prolonged parasitemia, and 80% survived. Because mice do not express GNLY, GNLY-transgenic mice can be used to assess the in vivo importance of GNLY. Parasite clearance was accelerated in GNLY-transgenic mice and depletion of CD8+ T cells ablated the GNLY-mediated resistance to P. yoelii. Altogether, our results indicate that in addition to previously described mechanisms, IFN-gamma promotes host resistance to the Retic-tropic P. yoelii 17XNL strain by promoting MHC-I expression on iRetics that become targets for CD8+ cytotoxic T lymphocytes and GNLY.</p>
dc.identifier.submissionpathoapubs/4374
dc.contributor.departmentDepartment of Medicine, Division of Infectious Diseases and Immunology
dc.source.pagese1008840


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Copyright © 2020 Hojo-Souza et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Except where otherwise noted, this item's license is described as Copyright © 2020 Hojo-Souza et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.