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Publication
Contributions of IFN-? and granulysin to the clearance of Plasmodium yoelii
blood stage.
Authors Hojo-Souza NS, de Azevedo PO, de Castro JT, Teixeira-Carvalho A, Lieberman J,
Junqueira C, Gazzinelli RT
Submitted By Submitted Externally on 10/12/2020
Status Published
Journal PLoS pathogens
Year 2020
Date Published 9/1/2020
Volume : Pages 16 : e1008840
PubMed Reference 32913355
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-?-producing T cells that form immune synapses with iRetics.
We now provide evidence that MHC-I expression by iRetic is dependent on
IFN-?-induced transcription of IRF-1, MHC-I and ß2-microglobulin (ß2-m) in
erythroblasts. Consistently, CTLs from infected wild type (WT) mice formed
immune synapses with iRetics in an IFN-?- and MHC-I-dependent manner. When
challenged with P. yoelii 17XNL, WT mice cleared parasitemia and survived, while
IFN-? KO mice remained parasitemic and all died. ß2-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-? 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.





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