PMID- 32913355
OWN - NLM
STAT- MEDLINE
DCOM- 20201013
LR  - 20220716
IS  - 1553-7374 (Electronic)
IS  - 1553-7366 (Print)
IS  - 1553-7366 (Linking)
VI  - 16
IP  - 9
DP  - 2020 Sep
TI  - Contributions of IFN-gamma and granulysin to the clearance of Plasmodium yoelii blood 
      stage.
PG  - e1008840
LID - 10.1371/journal.ppat.1008840 [doi]
LID - e1008840
AB  - 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.
FAU - Hojo-Souza, Natalia Satchiko
AU  - Hojo-Souza NS
AD  - Laboratorio de Imunopatologia, Instituto Rene Rachou, Fundacao Oswaldo Cruz, Belo 
      Horizonte, MG, Brazil.
FAU - de Azevedo, Patrick Orestes
AU  - de Azevedo PO
AD  - Laboratorio de Imunopatologia, Instituto Rene Rachou, Fundacao Oswaldo Cruz, Belo 
      Horizonte, MG, Brazil.
FAU - de Castro, Julia Teixeira
AU  - de Castro JT
AUID- ORCID: 0000-0003-2620-328X
AD  - Laboratorio de Imunopatologia, Instituto Rene Rachou, Fundacao Oswaldo Cruz, Belo 
      Horizonte, MG, Brazil.
AD  - Departamento de Bioquimica e Imunologia, Universidade Federal de Minas Gerais, 
      Belo Horizonte, MG, Brazil.
FAU - Teixeira-Carvalho, Andrea
AU  - Teixeira-Carvalho A
AD  - Grupo Integrado de Pesquisas em Biomarcadores, Instituto Rene Rachou, Fundacao 
      Oswaldo Cruz, Belo Horizonte, MG, Brazil.
FAU - Lieberman, Judy
AU  - Lieberman J
AUID- ORCID: 0000-0002-6200-4715
AD  - Program in Cellular and Molecular Medicine, Boston Children's Hospital and 
      Department of Pediatrics, Harvard Medical School, Boston, MA, United States of 
      America.
FAU - Junqueira, Caroline
AU  - Junqueira C
AUID- ORCID: 0000-0003-0545-0986
AD  - Laboratorio de Imunopatologia, Instituto Rene Rachou, Fundacao Oswaldo Cruz, Belo 
      Horizonte, MG, Brazil.
AD  - Program in Cellular and Molecular Medicine, Boston Children's Hospital and 
      Department of Pediatrics, Harvard Medical School, Boston, MA, United States of 
      America.
FAU - Gazzinelli, Ricardo Tostes
AU  - Gazzinelli RT
AUID- ORCID: 0000-0003-2427-7699
AD  - Laboratorio de Imunopatologia, Instituto Rene Rachou, Fundacao Oswaldo Cruz, Belo 
      Horizonte, MG, Brazil.
AD  - Division of Infectious Disease and Immunology, University of Massachusetts 
      Medical School, Worcester, MA, United States of America.
AD  - Plataforma de Medicina Translacional, Fundacao Oswaldo Cruz, Ribeirao Preto, SP, 
      Brazil.
LA  - eng
GR  - R01 AI079293/AI/NIAID NIH HHS/United States
GR  - R21 AI131632/AI/NIAID NIH HHS/United States
GR  - R21 AI150546/AI/NIAID NIH HHS/United States
GR  - U19 AI089681/AI/NIAID NIH HHS/United States
GR  - R01 NS098747/NS/NINDS NIH HHS/United States
GR  - U2C DK093000/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20200910
PL  - United States
TA  - PLoS Pathog
JT  - PLoS pathogens
JID - 101238921
RN  - 0 (Antigens, Differentiation, T-Lymphocyte)
RN  - 0 (GNLY protein, human)
RN  - 0 (IFNG protein, mouse)
RN  - 82115-62-6 (Interferon-gamma)
SB  - IM
MH  - Animals
MH  - Antigens, Differentiation, T-Lymphocyte/genetics/*immunology
MH  - CD8-Positive T-Lymphocytes/*immunology/pathology
MH  - Interferon-gamma/genetics/*immunology
MH  - Malaria/genetics/*immunology/pathology
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Mice, Knockout
MH  - Plasmodium yoelii/*immunology
PMC - PMC7482970
COIS- The authors have declared that no competing interests exist.
EDAT- 2020/09/12 06:00
MHDA- 2020/10/21 06:00
PMCR- 2020/09/10
CRDT- 2020/09/11 05:43
PHST- 2019/12/02 00:00 [received]
PHST- 2020/07/24 00:00 [accepted]
PHST- 2020/09/11 05:43 [entrez]
PHST- 2020/09/12 06:00 [pubmed]
PHST- 2020/10/21 06:00 [medline]
PHST- 2020/09/10 00:00 [pmc-release]
AID - PPATHOGENS-D-19-02236 [pii]
AID - 10.1371/journal.ppat.1008840 [doi]
PST - epublish
SO  - PLoS Pathog. 2020 Sep 10;16(9):e1008840. doi: 10.1371/journal.ppat.1008840. 
      eCollection 2020 Sep.