Multimodally profiling memory T cells from a tuberculosis cohort identifies cell state associations with demographics, environment and disease.
Nat Immunol
; 22(6): 781-793, 2021 06.
Article
en En
| MEDLINE
| ID: mdl-34031617
ABSTRACT
Multimodal T cell profiling can enable more precise characterization of elusive cell states underlying disease. Here, we integrated single-cell RNA and surface protein data from 500,089 memory T cells to define 31 cell states from 259 individuals in a Peruvian tuberculosis (TB) progression cohort. At immune steady state >4 years after infection and disease resolution, we found that, after accounting for significant effects of age, sex, season and genetic ancestry on T cell composition, a polyfunctional type 17 helper T (TH17) cell-like effector state was reduced in abundance and function in individuals who previously progressed from Mycobacterium tuberculosis (M.tb) infection to active TB disease. These cells are capable of responding to M.tb peptides. Deconvoluting this state-uniquely identifiable with multimodal analysis-from public data demonstrated that its depletion may precede and persist beyond active disease. Our study demonstrates the power of integrative multimodal single-cell profiling to define cell states relevant to disease and other traits.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Tuberculosis Pulmonar
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Células Th17
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Memoria Inmunológica
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Mycobacterium tuberculosis
Tipo de estudio:
Clinical_trials
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Observational_studies
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Prognostic_studies
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Risk_factors_studies
Límite:
Adolescent
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Adult
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Aged
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Aged80
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Child
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Female
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Humans
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Male
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Middle aged
País como asunto:
America do sul
/
Peru
Idioma:
En
Año:
2021
Tipo del documento:
Article