Immune responses in beta-thalassaemia: heme oxygenase 1 reduces cytokine production and bactericidal activity of human leucocytes.
Adult
Aged
Burkholderia pseudomallei
/ immunology
Cells, Cultured
Female
Healthy Volunteers
Heme Oxygenase-1
/ genetics
Humans
Immune Tolerance
Interferon-gamma
/ metabolism
Interleukin-10
/ metabolism
Leukocytes, Mononuclear
/ immunology
Male
Melioidosis
/ immunology
Middle Aged
Primary Cell Culture
RNA, Messenger
/ isolation & purification
Real-Time Polymerase Chain Reaction
Thailand
Young Adult
beta-Thalassemia
/ blood
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
24 06 2020
24 06 2020
Historique:
received:
18
12
2019
accepted:
08
06
2020
entrez:
26
6
2020
pubmed:
26
6
2020
medline:
22
12
2020
Statut:
epublish
Résumé
Patients with beta-thalassaemia increase the risk of bacterial infections, particularly Burkholderia pseudomallei (Bp), the causative agent of melioidosis in Thailand. Impaired immune cell functions may be the cause of this susceptibility, but detailed mechanisms have not been defined. In this study, we observed impaired production of IFN-gamma and IL-10 by whole blood from beta-thalassaemia patients upon stimulation with a range of bacteria-derived stimuli. In contrast, IFN-gamma response via TCR and plasma IgG specific for Bp were still intact. Importantly, mRNA expression of heme oxygenase 1 (HO-1), a potential modulator of immune function, was increased in whole blood from beta-thalassaemia patients, either with or without stimulation with Bp in vitro. Induction of HO-1 by hemin or CoPP in vitro reduced production of IFN-gamma and IL-10 from healthy human PBMCs and decreased bacterial clearance activity of whole blood from healthy controls and beta-thalassaemia, while inhibition of HO-1 by SnPP enhanced both functions in healthy controls. These results were confirmed to some extent in purified human monocytes of healthy controls. Our results suggest a mechanism that excess hemin of beta-thalassaemia patients is a significant cause of immune suppression via HO-1 induction and may underlie the susceptibility of these individuals to severe bacterial infection.
Identifiants
pubmed: 32581238
doi: 10.1038/s41598-020-67346-2
pii: 10.1038/s41598-020-67346-2
pmc: PMC7314746
doi:
Substances chimiques
IFNG protein, human
0
IL10 protein, human
0
RNA, Messenger
0
Interleukin-10
130068-27-8
Interferon-gamma
82115-62-6
HMOX1 protein, human
EC 1.14.14.18
Heme Oxygenase-1
EC 1.14.14.18
Types de publication
Journal Article
Observational Study
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
10297Références
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