Contributions of IFN-gamma and granulysin to the clearance of Plasmodium yoelii blood stage
Authors
Hojo-Souza, Natalia Satchikode Azevedo, Patrick Orestes
de Castro, Julia Teixeira
Teixeira-Carvalho, Andrea
Lieberman, Judy
Junqueira, Caroline
Gazzinelli, Ricardo T.
UMass Chan Affiliations
Department of Medicine, Division of Infectious Diseases and ImmunologyDocument Type
Journal ArticlePublication Date
2020-09-10Keywords
T cellsCytotoxic T cells
Plasmodium yoelii
Erythroblasts
Parasitic diseases
Parasitemia
Spleen
Blood
Amino Acids, Peptides, and Proteins
Enzymes and Coenzymes
Hemic and Immune Systems
Immunology of Infectious Disease
Parasitic Diseases
Parasitology
Pathogenic Microbiology
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Show full item recordAbstract
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.Source
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. Link to article on publisher's site
DOI
10.1371/journal.ppat.1008840Permanent Link to this Item
http://hdl.handle.net/20.500.14038/41585PubMed ID
32913355Related Resources
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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.Distribution License
http://creativecommons.org/licenses/by/4.0/ae974a485f413a2113503eed53cd6c53
10.1371/journal.ppat.1008840
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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.