HIV-1-induced cytokines deplete homeostatic innate lymphoid cells and expand TCF7-dependent memory NK cells.
Cytokines
/ blood
Gene Expression Regulation
HIV Infections
/ genetics
HIV-1
/ immunology
Homeostasis
/ immunology
Humans
Immunity, Innate
Immunologic Memory
In Vitro Techniques
Inflammation
/ genetics
Killer Cells, Natural
/ immunology
Lymphocytes
/ immunology
T Cell Transcription Factor 1
/ genetics
Wnt Signaling Pathway
/ immunology
Journal
Nature immunology
ISSN: 1529-2916
Titre abrégé: Nat Immunol
Pays: United States
ID NLM: 100941354
Informations de publication
Date de publication:
03 2020
03 2020
Historique:
received:
11
01
2019
accepted:
28
12
2019
pubmed:
19
2
2020
medline:
21
4
2020
entrez:
19
2
2020
Statut:
ppublish
Résumé
Human immunodeficiency virus 1 (HIV-1) infection is associated with heightened inflammation and excess risk of cardiovascular disease, cancer and other complications. These pathologies persist despite antiretroviral therapy. In two independent cohorts, we found that innate lymphoid cells (ILCs) were depleted in the blood and gut of people with HIV-1, even with effective antiretroviral therapy. ILC depletion was associated with neutrophil infiltration of the gut lamina propria, type 1 interferon activation, increased microbial translocation and natural killer (NK) cell skewing towards an inflammatory state, with chromatin structure and phenotype typical of WNT transcription factor TCF7-dependent memory T cells. Cytokines that are elevated during acute HIV-1 infection reproduced the ILC and NK cell abnormalities ex vivo. These results show that inflammatory cytokines associated with HIV-1 infection irreversibly disrupt ILCs. This results in loss of gut epithelial integrity, microbial translocation and memory NK cells with heightened inflammatory potential, and explains the chronic inflammation in people with HIV-1.
Identifiants
pubmed: 32066947
doi: 10.1038/s41590-020-0593-9
pii: 10.1038/s41590-020-0593-9
pmc: PMC7044076
mid: NIHMS1547618
doi:
Substances chimiques
Cytokines
0
T Cell Transcription Factor 1
0
TCF7 protein, human
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
274-286Subventions
Organisme : NIH HHS
ID : P51 OD011092
Pays : United States
Organisme : NIAID NIH HHS
ID : U19 AI096109
Pays : United States
Organisme : NIAID NIH HHS
ID : P30 AI042845
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR001453
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI111809
Pays : United States
Organisme : NIAID NIH HHS
ID : R24 AI067039
Pays : United States
Organisme : NIDA NIH HHS
ID : DP1 DA034990
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK105837
Pays : United States
Organisme : NIAID NIH HHS
ID : P30 AI027763
Pays : United States
Organisme : NIAID NIH HHS
ID : R21 AI119885
Pays : United States
Organisme : NHGRI NIH HHS
ID : U01 HG007910
Pays : United States
Organisme : NIAID NIH HHS
ID : R37 AI147868
Pays : United States
Organisme : NIH HHS
ID : S10 OD025002
Pays : United States
Commentaires et corrections
Type : CommentIn
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