Distinct blood transcriptomic signature of treatment in latent tuberculosis infected individuals at risk of developing active disease

Although only a small fraction will ever develop the active form of tuberculosis (ATB) disease, chemoprophylaxis treatment in latent TB infected (LTBI) individuals is an effective strategy to control pathogen transmission. Characterizing immune responses in LTBI upon chemoprophylactic treatment is i...

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Vydané v:Tuberculosis (Edinburgh, Scotland) Ročník 131; s. 102127
Hlavní autori: Burel, Julie G., Singhania, Akul, Dubelko, Paige, Muller, Julius, Tanner, Rachel, Parizotto, Eneida, Dedicoat, Martin, Fletcher, Thomas E., Dunbar, James, Cunningham, Adam F., Lindestam Arlehamn, Cecilia S., Catanzaro, Donald G., Catanzaro, Antonino, Rodwell, Timothy, McShane, Helen, O'Shea, Matthew K., Peters, Bjoern
Médium: Journal Article
Jazyk:English
Vydavateľské údaje: Scotland Elsevier Ltd 01.12.2021
Elsevier Science Ltd
Predmet:
Adult
Blood
Blood transcriptomics
Case-Control Studies
England
Female
Gene expression
Gene Expression Profiling - methods
Gene Expression Profiling - statistics & numerical data
Humans
Immune response
Interferon
Latent tuberculosis
Latent Tuberculosis - blood
Latent Tuberculosis - genetics
Longitudinal Studies
Male
Middle Aged
Mycobacterium tuberculosis - drug effects
Mycobacterium tuberculosis - growth & development
Prophylaxis treatment
Risk
Signatures
State Medicine - organization & administration
State Medicine - statistics & numerical data
Tissue Array Analysis - methods
Tissue Array Analysis - statistics & numerical data
Transcriptome - genetics
Transcriptome - immunology
Transcriptomes
Transcriptomics
Tuberculosis
England
Blood transcriptomics
Latent tuberculosis
Prophylaxis treatment
ISSN:1472-9792, 1873-281X, 1873-281X
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Shrnutí:Although only a small fraction will ever develop the active form of tuberculosis (ATB) disease, chemoprophylaxis treatment in latent TB infected (LTBI) individuals is an effective strategy to control pathogen transmission. Characterizing immune responses in LTBI upon chemoprophylactic treatment is important to facilitate treatment monitoring, and thus improve TB control strategies. Here, we studied changes in the blood transcriptome in a cohort of 42 LTBI and 8 ATB participants who received anti-TB therapy. Based on the expression of previously published gene signatures of progression to ATB, we stratified the LTBI cohort in two groups and examined if individuals deemed to be at elevated risk of developing ATB before treatment (LTBI-Risk) differed from others (LTBI-Other). We found that LTBI-Risk and LTBI-Other groups were associated with two distinct transcriptomic treatment signatures, with the LTBI-Risk signature resembling that of treated ATB patients. Notably, overlapping genes between LTBI-Risk and ATB treatment signatures were associated with risk of progression to ATB and interferon (IFN) signaling, and were selectively downregulated upon treatment in the LTBI-Risk but not the LTBI-Other group. Our results suggest that transcriptomic reprogramming following treatment of LTBI is heterogeneous and can be used to distinguish LTBI-Risk individuals from the LTBI cohort at large.
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MKO conceived and designed the study. RT and EP conducted the experiments. JGB, MKO and BP led the data analysis and interpretation with input from all authors. JGB, MKO and BP wrote the manuscript and all authors edited the manuscript.
Author contributions
ISSN:1472-9792
1873-281X
1873-281X
DOI:10.1016/j.tube.2021.102127