Contributions of IFN-γ and granulysin to the clearance of Plasmodium yoelii blood stage.
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 infect...
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Online Access: | https://doi.org/10.1371/journal.ppat.1008840 |
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doaj-3136948f2d3a46078d7944b6bb317b002021-04-21T17:16:33ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742020-09-01169e100884010.1371/journal.ppat.1008840Contributions of IFN-γ and granulysin to the clearance of Plasmodium yoelii blood stage.Natália Satchiko Hojo-SouzaPatrick Orestes de AzevedoJúlia Teixeira de CastroAndréa Teixeira-CarvalhoJudy LiebermanCaroline JunqueiraRicardo Tostes GazzinelliP. 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-γ-producing T cells that form immune synapses with iRetics. We now provide evidence that MHC-I expression by iRetic is dependent on IFN-γ-induced transcription of IRF-1, MHC-I and β2-microglobulin (β2-m) in erythroblasts. Consistently, CTLs from infected wild type (WT) mice formed immune synapses with iRetics in an IFN-γ- and MHC-I-dependent manner. When challenged with P. yoelii 17XNL, WT mice cleared parasitemia and survived, while IFN-γ KO mice remained parasitemic and all died. β2-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-γ 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.https://doi.org/10.1371/journal.ppat.1008840 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Natália Satchiko Hojo-Souza Patrick Orestes de Azevedo Júlia Teixeira de Castro Andréa Teixeira-Carvalho Judy Lieberman Caroline Junqueira Ricardo Tostes Gazzinelli |
spellingShingle |
Natália Satchiko Hojo-Souza Patrick Orestes de Azevedo Júlia Teixeira de Castro Andréa Teixeira-Carvalho Judy Lieberman Caroline Junqueira Ricardo Tostes Gazzinelli Contributions of IFN-γ and granulysin to the clearance of Plasmodium yoelii blood stage. PLoS Pathogens |
author_facet |
Natália Satchiko Hojo-Souza Patrick Orestes de Azevedo Júlia Teixeira de Castro Andréa Teixeira-Carvalho Judy Lieberman Caroline Junqueira Ricardo Tostes Gazzinelli |
author_sort |
Natália Satchiko Hojo-Souza |
title |
Contributions of IFN-γ and granulysin to the clearance of Plasmodium yoelii blood stage. |
title_short |
Contributions of IFN-γ and granulysin to the clearance of Plasmodium yoelii blood stage. |
title_full |
Contributions of IFN-γ and granulysin to the clearance of Plasmodium yoelii blood stage. |
title_fullStr |
Contributions of IFN-γ and granulysin to the clearance of Plasmodium yoelii blood stage. |
title_full_unstemmed |
Contributions of IFN-γ and granulysin to the clearance of Plasmodium yoelii blood stage. |
title_sort |
contributions of ifn-γ and granulysin to the clearance of plasmodium yoelii blood stage. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS Pathogens |
issn |
1553-7366 1553-7374 |
publishDate |
2020-09-01 |
description |
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-γ-producing T cells that form immune synapses with iRetics. We now provide evidence that MHC-I expression by iRetic is dependent on IFN-γ-induced transcription of IRF-1, MHC-I and β2-microglobulin (β2-m) in erythroblasts. Consistently, CTLs from infected wild type (WT) mice formed immune synapses with iRetics in an IFN-γ- and MHC-I-dependent manner. When challenged with P. yoelii 17XNL, WT mice cleared parasitemia and survived, while IFN-γ KO mice remained parasitemic and all died. β2-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-γ 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. |
url |
https://doi.org/10.1371/journal.ppat.1008840 |
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