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Glibenclamide Reduces Primary Human Monocyte Functions Against Tuberculosis Infection by Enhancing M2 Polarization
- Source :
- Frontiers in Immunology, Vol 9 (2018), Frontiers in Immunology
- Publication Year :
- 2018
- Publisher :
- Frontiers Media S.A., 2018.
-
Abstract
- Tuberculosis (TB) is a global public health problem, which is caused by Mycobacterium tuberculosis (Mtb). Type 2 diabetes mellitus (T2DM) is one of the leading predisposing factors for development of TB after HIV/AIDS. Glibenclamide is a widely used anti-diabetic drug in low and middle-income countries where the incidence of TB is very high. In a human macrophage cell line, glibenclamide, a K+ATP-channel blocker, promoted alternative activation of macrophages by enhancing expression of the M2 marker CD206 during M2 polarization. M2 macrophages are considered poorly microbicidal and associated with TB susceptibility. Here, we investigated the effect of glibenclamide on M1 and M2 phenotypes of primary human monocytes and further determined whether specific drug treatment for T2DM individuals influences the antibacterial function of monocytes in response to mycobacterial infection. We found that glibenclamide significantly reduced M1 (HLA-DR+ and CD86+) surface markers and TNF-α production on primary human monocytes against mycobacterial infection. In contrast, M2 (CD163+ and CD206+) surface markers and IL-10 production were enhanced by pretreatment with glibenclamide. Additionally, reduction of bactericidal activity also occurred when primary human monocytes from T2DM individuals who were being treated with glibenclamide were infected with Mtb in vitro, consistent with the cytokine responses. We conclude that glibenclamide reduces M1 and promotes M2 polarization leading to impaired bactericidal ability of primary human monocytes of T2DM individuals in response to Mtb and may lead to increased susceptibility of T2DM individuals to TB and other bacterial infectious diseases.
- Subjects :
- Male
0301 basic medicine
medicine.medical_treatment
Monocytes
Glibenclamide
Glyburide
Immunology and Allergy
Medicine
Cells, Cultured
Original Research
biology
M2 polarization
Middle Aged
Cytokine
medicine.anatomical_structure
glibenclamide
monocyte
diabetes mellitus
Female
Mannose Receptor
medicine.drug
Adult
lcsh:Immunologic diseases. Allergy
Tuberculosis
Immunology
Receptors, Cell Surface
Mycobacterium tuberculosis
03 medical and health sciences
Humans
Hypoglycemic Agents
Lectins, C-Type
Aged
CD86
business.industry
Macrophages
Monocyte
Macrophage Activation
biology.organism_classification
medicine.disease
In vitro
Mannose-Binding Lectins
030104 developmental biology
Diabetes Mellitus, Type 2
anti-diabetic drug
business
lcsh:RC581-607
CD163
Subjects
Details
- Language :
- English
- ISSN :
- 16643224
- Volume :
- 9
- Database :
- OpenAIRE
- Journal :
- Frontiers in Immunology
- Accession number :
- edsair.doi.dedup.....9f37c0a82f3768e076d777f4a6bd6e94