Abstract
Rationale: Individuals with a history of tuberculosis (TB) disease are at elevated risk of disease recurrence. The underlying cause is not known, but one explanation is that previous disease results in less-effective immunity against Mycobacterium tuberculosis (Mtb). Objectives: We hypothesized that the repertoire of Mtb-derived epitopes recognized by T cells from individuals with latent Mtb infection differs as a function of previous diagnosis of active TB disease. Methods: T-cell responses to peptide pools in samples collected from an adult screening and an adolescent validation cohort were measured by IFN-g enzyme-linked immunospot assay or intracellular cytokine staining. Measurements and Main Results: We identified a set of “type 2” T-cell epitopes that were recognized at 10-fold–lower levels in Mtb-infected individuals with a history of TB disease less than 6 years ago than in those withou previous TB. By contrast, “type 1” epitopes were recognized equally well in individuals with or without previous TB. The differential epitope recognition was not due to differences in HLA class II binding, memory phenotypes, or gene expression in the responding T cells. Instead, “TB disease histor sensitive” type 2 epitopes were significantly (P, 0.0001) more homologous to sequences from bacteria found in the human microbiome than type 1 epitopes. Conclusions: Preferential loss of T-cell reactivity to Mtb epitopes that are homologous to bacteria in the microbiome in persons with previous TB disease may reflect long-term effects of antibiotic TB treatment on the microbiome.
| Original language | English |
|---|---|
| Pages (from-to) | 772-781 |
| Number of pages | 10 |
| Journal | American Journal of Respiratory and Critical Care Medicine |
| Volume | 196 |
| Issue number | 6 |
| DOIs | |
| Publication status | Published - Sep 15 2017 |
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Keywords
- Adaptive immunity
- Microbiome
- Mycobacterium tuberculosis
- T-cell epitopes
- Tuberculosis
ASJC Scopus subject areas
- Pulmonary and Respiratory Medicine
- Critical Care and Intensive Care Medicine
Cite this
Differential recognition of mycobacterium tuberculosis–specific epitopes as a function of tuberculosis disease history. / Scriba, Thomas J.; Carpenter, Chelsea; Pro, Sebastian Carrasco; Sidney, John; Musvosvi, Munyaradzi; Rozot, Virginie; Seumois, Grégory; Rosales, Sandy L.; Vijayanand, Pandurangan; Goletti, Delia; Makgotlho, Edward; Hanekom, Willem; Hatherill, Mark; Peters, Bjoern; Sette, Alessandro; Arlehamn, Cecilia S.Lindestam.
In: American Journal of Respiratory and Critical Care Medicine, Vol. 196, No. 6, 15.09.2017, p. 772-781.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Differential recognition of mycobacterium tuberculosis–specific epitopes as a function of tuberculosis disease history
AU - Scriba, Thomas J.
AU - Carpenter, Chelsea
AU - Pro, Sebastian Carrasco
AU - Sidney, John
AU - Musvosvi, Munyaradzi
AU - Rozot, Virginie
AU - Seumois, Grégory
AU - Rosales, Sandy L.
AU - Vijayanand, Pandurangan
AU - Goletti, Delia
AU - Makgotlho, Edward
AU - Hanekom, Willem
AU - Hatherill, Mark
AU - Peters, Bjoern
AU - Sette, Alessandro
AU - Arlehamn, Cecilia S.Lindestam
PY - 2017/9/15
Y1 - 2017/9/15
N2 - Rationale: Individuals with a history of tuberculosis (TB) disease are at elevated risk of disease recurrence. The underlying cause is not known, but one explanation is that previous disease results in less-effective immunity against Mycobacterium tuberculosis (Mtb). Objectives: We hypothesized that the repertoire of Mtb-derived epitopes recognized by T cells from individuals with latent Mtb infection differs as a function of previous diagnosis of active TB disease. Methods: T-cell responses to peptide pools in samples collected from an adult screening and an adolescent validation cohort were measured by IFN-g enzyme-linked immunospot assay or intracellular cytokine staining. Measurements and Main Results: We identified a set of “type 2” T-cell epitopes that were recognized at 10-fold–lower levels in Mtb-infected individuals with a history of TB disease less than 6 years ago than in those withou previous TB. By contrast, “type 1” epitopes were recognized equally well in individuals with or without previous TB. The differential epitope recognition was not due to differences in HLA class II binding, memory phenotypes, or gene expression in the responding T cells. Instead, “TB disease histor sensitive” type 2 epitopes were significantly (P, 0.0001) more homologous to sequences from bacteria found in the human microbiome than type 1 epitopes. Conclusions: Preferential loss of T-cell reactivity to Mtb epitopes that are homologous to bacteria in the microbiome in persons with previous TB disease may reflect long-term effects of antibiotic TB treatment on the microbiome.
AB - Rationale: Individuals with a history of tuberculosis (TB) disease are at elevated risk of disease recurrence. The underlying cause is not known, but one explanation is that previous disease results in less-effective immunity against Mycobacterium tuberculosis (Mtb). Objectives: We hypothesized that the repertoire of Mtb-derived epitopes recognized by T cells from individuals with latent Mtb infection differs as a function of previous diagnosis of active TB disease. Methods: T-cell responses to peptide pools in samples collected from an adult screening and an adolescent validation cohort were measured by IFN-g enzyme-linked immunospot assay or intracellular cytokine staining. Measurements and Main Results: We identified a set of “type 2” T-cell epitopes that were recognized at 10-fold–lower levels in Mtb-infected individuals with a history of TB disease less than 6 years ago than in those withou previous TB. By contrast, “type 1” epitopes were recognized equally well in individuals with or without previous TB. The differential epitope recognition was not due to differences in HLA class II binding, memory phenotypes, or gene expression in the responding T cells. Instead, “TB disease histor sensitive” type 2 epitopes were significantly (P, 0.0001) more homologous to sequences from bacteria found in the human microbiome than type 1 epitopes. Conclusions: Preferential loss of T-cell reactivity to Mtb epitopes that are homologous to bacteria in the microbiome in persons with previous TB disease may reflect long-term effects of antibiotic TB treatment on the microbiome.
KW - Adaptive immunity
KW - Microbiome
KW - Mycobacterium tuberculosis
KW - T-cell epitopes
KW - Tuberculosis
UR - http://www.scopus.com/inward/record.url?scp=85029708020&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85029708020&partnerID=8YFLogxK
U2 - 10.1164/rccm.201706-1208OC
DO - 10.1164/rccm.201706-1208OC
M3 - Article
VL - 196
SP - 772
EP - 781
JO - American Journal of Respiratory and Critical Care Medicine
JF - American Journal of Respiratory and Critical Care Medicine
SN - 1073-449X
IS - 6
ER -