UMMS Affiliation

Department of Medicine, Division of Infectious Diseases and Immunology

Publication Date

2020-09-10

Document Type

Article

Disciplines

Amino Acids, Peptides, and Proteins | Enzymes and Coenzymes | Hemic and Immune Systems | Immunology of Infectious Disease | Parasitic Diseases | Parasitology | Pathogenic Microbiology

Abstract

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.

Keywords

T cells, Cytotoxic T cells, Plasmodium yoelii, Erythroblasts, Parasitic diseases, Parasitemia, Spleen, Blood

Rights and Permissions

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.

DOI of Published Version

10.1371/journal.ppat.1008840

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

Journal/Book/Conference Title

PLoS pathogens

Related Resources

Link to Article in PubMed

PubMed ID

32913355

Creative Commons License

Creative Commons Attribution 4.0 License
This work is licensed under a Creative Commons Attribution 4.0 License.

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