Impact of Intermediate Hyperglycemia and Diabetes on Immune Dysfunction in Tuberculosis.

Diabetes Mellitus Humans Hyperglycemia / complications Indonesia Mycobacterium tuberculosis Peru South Africa / epidemiology Tuberculosis / complications Tuberculosis, Pulmonary
diabetes hyperglycemia inflammation tuberculosis

Journal

Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
ISSN: 1537-6591
Titre abrégé: Clin Infect Dis
Pays: United States
ID NLM: 9203213

Informations de publication

Date de publication:
23 01 2021
Historique:
received: 03 01 2020
accepted: 09 06 2020
pubmed: 14 6 2020
medline: 29 4 2021
entrez: 14 6 2020
Statut: ppublish

Résumé

People with diabetes have an increased risk of developing active tuberculosis (TB) and are more likely to have poor TB-treatment outcomes, which may impact on control of TB as the prevalence of diabetes is increasing worldwide. Blood transcriptomes are altered in patients with active TB relative to healthy individuals. The effects of diabetes and intermediate hyperglycemia (IH) on this transcriptomic signature were investigated to enhance understanding of immunological susceptibility in diabetes-TB comorbidity. Whole blood samples were collected from active TB patients with diabetes (glycated hemoglobin [HbA1c] ≥6.5%) or IH (HbA1c = 5.7% to <6.5%), TB-only patients, and healthy controls in 4 countries: South Africa, Romania, Indonesia, and Peru. Differential blood gene expression was determined by RNA-seq (n = 249). Diabetes increased the magnitude of gene expression change in the host transcriptome in TB, notably showing an increase in genes associated with innate inflammatory and decrease in adaptive immune responses. Strikingly, patients with IH and TB exhibited blood transcriptomes much more similar to patients with diabetes-TB than to patients with only TB. Both diabetes-TB and IH-TB patients had a decreased type I interferon response relative to TB-only patients. Comorbidity in individuals with both TB and diabetes is associated with altered transcriptomes, with an expected enhanced inflammation in the presence of both conditions, but also reduced type I interferon responses in comorbid patients, suggesting an unexpected uncoupling of the TB transcriptome phenotype. These immunological dysfunctions are also present in individuals with IH, showing that altered immunity to TB may also be present in this group. The TB disease outcomes in individuals with IH diagnosed with TB should be investigated further.

Sections du résumé

BACKGROUND
People with diabetes have an increased risk of developing active tuberculosis (TB) and are more likely to have poor TB-treatment outcomes, which may impact on control of TB as the prevalence of diabetes is increasing worldwide. Blood transcriptomes are altered in patients with active TB relative to healthy individuals. The effects of diabetes and intermediate hyperglycemia (IH) on this transcriptomic signature were investigated to enhance understanding of immunological susceptibility in diabetes-TB comorbidity.
METHODS
Whole blood samples were collected from active TB patients with diabetes (glycated hemoglobin [HbA1c] ≥6.5%) or IH (HbA1c = 5.7% to <6.5%), TB-only patients, and healthy controls in 4 countries: South Africa, Romania, Indonesia, and Peru. Differential blood gene expression was determined by RNA-seq (n = 249).
RESULTS
Diabetes increased the magnitude of gene expression change in the host transcriptome in TB, notably showing an increase in genes associated with innate inflammatory and decrease in adaptive immune responses. Strikingly, patients with IH and TB exhibited blood transcriptomes much more similar to patients with diabetes-TB than to patients with only TB. Both diabetes-TB and IH-TB patients had a decreased type I interferon response relative to TB-only patients.
CONCLUSIONS
Comorbidity in individuals with both TB and diabetes is associated with altered transcriptomes, with an expected enhanced inflammation in the presence of both conditions, but also reduced type I interferon responses in comorbid patients, suggesting an unexpected uncoupling of the TB transcriptome phenotype. These immunological dysfunctions are also present in individuals with IH, showing that altered immunity to TB may also be present in this group. The TB disease outcomes in individuals with IH diagnosed with TB should be investigated further.

Identifiants

DOI: 10.1093/cid/ciaa751 PMID: 32533832 PMC: PMC7823074
pubmed: 32533832
pii: 5857148
doi: 10.1093/cid/ciaa751
pmc: PMC7823074
doi:

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

69-78

Subventions

Organisme : Medical Research Council
ID : MC_PC_17218
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/P017568/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/R005850/1
Pays : United Kingdom

Investigateurs

H Dockrell (H)
J Cliff (J)
C Eckold (C)
D Moore (D)
U Griffiths (U)
Y Laurence (Y)
R Aarnouste (R)
M Netea (M)
R van Crevel (R)
C Ruesen (C)
E Lachmandas (E)
S Kaufmann (S)
M Beigier (M)
R Golinski (R)
S Joosten (S)
T Ottenhoff (T)
F Vrieling (F)
M Haks (M)
G Walzl (G)
K Ronacher (K)
S Malherbe (S)
L Kleynhans (L)
B Smith (B)
K Stanley (K)
G van der Spuy (G)
A Loxton (A)
N Chegou (N)
M Bosman (M)
L Thiart (L)
C Wagman (C)
H Tshivhula (H)
M Selamolela (M)
N Prins (N)
W du Plessis (W)
I van Rensburg (I)
L du Toit (L)
J Critchley (J)
S Kerry-Barnard (S)
F Pearson (F)
D Grint (D)
S McAllister (S)
P Hill (P)
A Verrall (A)
M Ioana (M)
A Riza (A)
R Cioboata (R)
M Dudau (M)
F Nitu (F)
I Bazavan (I)
M Olteanu (M)
C Editoiu (C)
A Florescu (A)
M Mota (M)
S G Popa (SG)
A Firanescu (A)
A Popa (A)
I Gheonea (I)
S Bicuti (S)
A Lepadat (A)
I Vladu (I)
D Clenciu (D)
M Bicu (M)
C Streba (C)
A Demetrian (A)
M Ciurea (M)
A Cimpoeru (A)
A Ciocoiu (A)
S Dorobantu (S)
R Plesea (R)
E L Popescu (EL)
M Cucu (M)
I Streata (I)
F Burada (F)
S Serban-Sosoi (S)
N Panduru (N)
E Nicoli (E)
M Ciontea (M)
I Capitanescu (I)
M Olaru (M)
T Tataru (T)
M Papurica (M)
I Valutanu (I)
V Dubreu (V)
L Stamatoiu (L)
V Kumar (V)
C Wijmenga (C)
C Ugarte-Gil (C)
J Coronel (J)
S Lopez (S)
R Limascca (R)
K Villaizan (K)
B Castro (B)
J Flores (J)
W Solano (W)
B Alisjahbana (B)
R Ruslami (R)
N Soetedjo (N)
P Santoso (P)
L Chaidir (L)
R Koesoemadinata (R)
N Susilawati (N)
J Annisa (J)
R Livia (R)
V Yunivita (V)
A Soeroto (A)
H Permana (H)
S Imaculata (S)
Y Gunawan (Y)
N Dewi (N)
L Apriani (L)

Informations de copyright

© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America.

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Auteurs

Clare Eckold (C)

Tuberculosis Centre and Department of Infection and Biology, London School of Hygiene and Tropical Medicine, London, United Kingdom.

Vinod Kumar (V)

University of Groningen, Department of Genetics, University Medical Center Groningen, Groningen, The Netherlands.
Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, The Netherlands.

January Weiner (J)

Max Planck Institute for Infection Biology, Berlin, Germany.

Bachti Alisjahbana (B)

TB-HIV Research Center, Faculty of Medicine, Universitas Padjadjaran, Bandung, Indonesia.
Hasan Sadikin General Hospital, Bandung, Indonesia.

Anca-Lelia Riza (AL)

Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, The Netherlands.
Human Genomics Laboratory, University of Medicine and Pharmacy, Craiova, Romania.
Regional Centre for Human Genetics-Dolj, Emergency Clinical County Hospital, Craiova, Romania.

Katharina Ronacher (K)

Mater Research Institute-University of Queensland, Translational Research Institute, Brisbane, Australia.
South Africa Medical Research Council Centre for Tuberculosis Research, Department of Science and Technology/National Research Foundation Centre of Excellence for Biomedical Tuberculosis Research, Division of Molecular Biology and Human Genetics, Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa.

Jorge Coronel (J)

Laboratorio de Investigación de Enfermedades Infecciosas, Universidad Peruana Cayetano Heredia, Lima, Peru.

Sarah Kerry-Barnard (S)

Population Health Research Institute, St George's, University of London, London, United Kingdom.

Stephanus T Malherbe (ST)

South Africa Medical Research Council Centre for Tuberculosis Research, Department of Science and Technology/National Research Foundation Centre of Excellence for Biomedical Tuberculosis Research, Division of Molecular Biology and Human Genetics, Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa.

Leanie Kleynhans (L)

South Africa Medical Research Council Centre for Tuberculosis Research, Department of Science and Technology/National Research Foundation Centre of Excellence for Biomedical Tuberculosis Research, Division of Molecular Biology and Human Genetics, Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa.

Kim Stanley (K)

South Africa Medical Research Council Centre for Tuberculosis Research, Department of Science and Technology/National Research Foundation Centre of Excellence for Biomedical Tuberculosis Research, Division of Molecular Biology and Human Genetics, Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa.

Rovina Ruslami (R)

TB-HIV Research Center, Faculty of Medicine, Universitas Padjadjaran, Bandung, Indonesia.

Mihai Ioana (M)

Human Genomics Laboratory, University of Medicine and Pharmacy, Craiova, Romania.
Regional Centre for Human Genetics-Dolj, Emergency Clinical County Hospital, Craiova, Romania.

Cesar Ugarte-Gil (C)

Tuberculosis Centre and Department of Infection and Biology, London School of Hygiene and Tropical Medicine, London, United Kingdom.
School of Medicine, Universidad Peruana Cayetano Heredia, Lima, Peru.

Gerhard Walzl (G)

South Africa Medical Research Council Centre for Tuberculosis Research, Department of Science and Technology/National Research Foundation Centre of Excellence for Biomedical Tuberculosis Research, Division of Molecular Biology and Human Genetics, Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa.

Reinout van Crevel (R)

Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, The Netherlands.

Cisca Wijmenga (C)

University of Groningen, Department of Genetics, University Medical Center Groningen, Groningen, The Netherlands.

Julia A Critchley (JA)

Population Health Research Institute, St George's, University of London, London, United Kingdom.

Hazel M Dockrell (HM)

Tuberculosis Centre and Department of Infection and Biology, London School of Hygiene and Tropical Medicine, London, United Kingdom.

Jacqueline M Cliff (JM)

Tuberculosis Centre and Department of Infection and Biology, London School of Hygiene and Tropical Medicine, London, United Kingdom.

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Classifications MeSH

questionsmedicales.fr › Maladies endocriniennes › Diabète › Impact of Intermediate Hyperglycemia and...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Impact of Intermediate Hyperglycemia and...
questionsmedicales.fr › Maladies métaboliques et nutritionnelles › Maladies métaboliques › Troubles du métabolisme du glucose › Hyperglycémie › Impact of Intermediate Hyperglycemia and...
questionsmedicales.fr › Régions géographiques › Iles › Indonésie › Impact of Intermediate Hyperglycemia and...
questionsmedicales.fr › Bactéries › Bactéries à Gram positif › Bâtonnets à Gram positif › Bâtonnets asporogènes à Gram positif › Bâtonnets asporogènes réguliers à Gram positif › Mycobacteriaceae › Mycobacterium › Mycobacterium tuberculosis › Impact of Intermediate Hyperglycemia and...
questionsmedicales.fr › Régions géographiques › Amériques › Amérique du Sud › Pérou › Impact of Intermediate Hyperglycemia and...
questionsmedicales.fr › Régions géographiques › Afrique › Afrique subsaharienne › Afrique australe › République d'Afrique du Sud › Impact of Intermediate Hyperglycemia and...
questionsmedicales.fr › Infection › Infections bactériennes et mycoses › Infections bactériennes › Infections bactériennes à Gram positif › Infections à Actinomycetales › Infections à Mycobacterium › Tuberculose › Impact of Intermediate Hyperglycemia and...
questionsmedicales.fr › Maladies de l'appareil respiratoire › Infections de l'appareil respiratoire › Tuberculose pulmonaire › Impact of Intermediate Hyperglycemia and...