γδ T cells suppress Plasmodium falciparum blood-stage infection by direct killing and phagocytosis.
Antigens, CD
/ metabolism
Antigens, Differentiation, T-Lymphocyte
/ metabolism
Antigens, Protozoan
/ blood
Boston
Brazil
Butyrophilins
/ metabolism
Cells, Cultured
Cytotoxicity, Immunologic
Erythrocytes
/ immunology
Female
Granzymes
/ metabolism
Host-Parasite Interactions
Humans
Immunological Synapses
/ metabolism
Intraepithelial Lymphocytes
/ immunology
Lymphocyte Activation
Malaria, Falciparum
/ blood
Male
Phagocytosis
Plasmodium falciparum
/ growth & development
Journal
Nature immunology
ISSN: 1529-2916
Titre abrégé: Nat Immunol
Pays: United States
ID NLM: 100941354
Informations de publication
Date de publication:
03 2021
03 2021
Historique:
received:
20
02
2020
accepted:
23
11
2020
pubmed:
13
1
2021
medline:
27
4
2021
entrez:
12
1
2021
Statut:
ppublish
Résumé
Activated Vγ9Vδ2 (γδ2) T lymphocytes that sense parasite-produced phosphoantigens are expanded in Plasmodium falciparum-infected patients. Although previous studies suggested that γδ2 T cells help control erythrocytic malaria, whether γδ2 T cells recognize infected red blood cells (iRBCs) was uncertain. Here we show that iRBCs stained for the phosphoantigen sensor butyrophilin 3A1 (BTN3A1). γδ2 T cells formed immune synapses and lysed iRBCs in a contact, phosphoantigen, BTN3A1 and degranulation-dependent manner, killing intracellular parasites. Granulysin released into the synapse lysed iRBCs and delivered death-inducing granzymes to the parasite. All intra-erythrocytic parasites were susceptible, but schizonts were most sensitive. A second protective γδ2 T cell mechanism was identified. In the presence of patient serum, γδ2 T cells phagocytosed and degraded opsonized iRBCs in a CD16-dependent manner, decreasing parasite multiplication. Thus, γδ2 T cells have two ways to control blood-stage malaria-γδ T cell antigen receptor (TCR)-mediated degranulation and phagocytosis of antibody-coated iRBCs.
Identifiants
pubmed: 33432229
doi: 10.1038/s41590-020-00847-4
pii: 10.1038/s41590-020-00847-4
pmc: PMC7906917
mid: NIHMS1649439
doi:
Substances chimiques
Antigens, CD
0
Antigens, Differentiation, T-Lymphocyte
0
Antigens, Protozoan
0
BTN2A1 protein, human
0
BTN3A1 protein, human
0
Butyrophilins
0
GNLY protein, human
0
GZMB protein, human
EC 3.4.21.-
Granzymes
EC 3.4.21.-
Types de publication
Journal Article
Multicenter Study
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
347-357Subventions
Organisme : NIAID NIH HHS
ID : R01 AI116577
Pays : United States
Organisme : NIAID NIH HHS
ID : R21 AI131632
Pays : United States
Organisme : NIAID NIH HHS
ID : U19 AI089681
Pays : United States
Organisme : NIAID NIH HHS
ID : R21 AI150546
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI145941
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS098747
Pays : United States
Commentaires et corrections
Type : CommentIn
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