PT  - JOURNAL ARTICLE
AU  - Pavlova, Ekaterina
AU  - Erokhina, Maria
TI  - Late Breaking Abstract - Bedaquiline enhances receptor phagocytosis and decreases IL1b production in human pro-inflammatory macrophages
AID  - 10.1183/13993003.congress-2021.PA2480
DP  - 2021 Sep 05
TA  - European Respiratory Journal
PG  - PA2480
VI  - 58
IP  - suppl 65
4099  - http://erj.ersjournals.com/content/58/suppl_65/PA2480.short
4100  - http://erj.ersjournals.com/content/58/suppl_65/PA2480.full
SO  - Eur Respir J2021 Sep 05; 58
AB  - Bedaquiline (BDQ) is one of the modern antibiotics for MDR-tuberculosis (TB) therapy. Its immunomodulatory properties have not yet been studied. The aim of our work was to reveal BDQ effects on the functional activity of pro-inflammatory (M1) human macrophages.BDQ effects (5 μg/ml) were assessed at different stages of M1-macrophage differentiation (MD) which was induced in THP-1 monocytic cell line by 100 nM PMA. We used RT-PCR to analyze genes expression of cytokines and key phagocytic receptors, multiplex analysis to determine the level of cytokines and flow cytometry to assess phagocytosis of mannan and IgG-latex beads.THP-1 M1 macrophages are characterized by the high levels of: (i) expression of TNF, IL1b and IL6 and Fc receptor (CD64) genes; (ii) production of TNF, IL1b and IL6 cytokines; (iii) phagocytosis activity of IgG latex beads. The phagocytosis receptor genes DC-SIGN (CD209) and MRC1 (CD206) are expressed at a low level. In the early stages of MD, BDQ significantly increased in the CD64 and CD209 gene expression and does not affect the CD206 expression. Also, under the BDQ, the cells phagocytic activity was elevated. Also, BDQ reduced IL1b gene expression by 2 times, and the level of the secreted cytokine - more than 6 times. No effects on the gene expression and secretion of TNF, IL6 and IL10 were found. The BDQ effects were less pronounced in the late stages of THP-1 MD, but the receptor phagocytosis was significantly increased.Thus, we revealed therapeutically valuable immunomodulatory BDQ effects on M1 macrophages: increase in receptor phagocytosis is important in the fight against pathogens and decrease of IL1b production to restrain TB inflammation.FootnotesCite this article as: European Respiratory Journal 2021; 58: Suppl. 65, PA2480.This abstract was presented at the 2021 ERS International Congress, in session “Prediction of exacerbations in patients with COPD”.This is an ERS International Congress abstract. No full-text version is available. Further material to accompany this abstract may be available at www.ers-education.org (ERS member access only).