TY - JOUR
T1 - Mycobacterial cord factor enhances migration of neutrophil-like HL-60 cells by prolonging AKT phosphorylation
AU - Lee, Wook Bin
AU - Yan, Ji Jing
AU - Kang, Ji Seon
AU - Chung, Seok
AU - Kim, Lark Kyun
N1 - Funding Information:
This research was supported by Basic Science Research Program through the NRF funded by the Ministry of Education (NRF-2016R1D1A1B01015292 to L.K.K.) and by a faculty research grant from Yonsei University College of Medicine (6-2017-0037 to L.K.K.). This research was also supported by a Basic Science Research Program through the NRF funded by the Ministry of Science, ICT & Future Planning (NRF-2016R1A6A3A11934835 to W.-B.L.).
Publisher Copyright:
© 2017 The Societies and John Wiley & Sons Australia, Ltd
PY - 2017/12
Y1 - 2017/12
N2 - Trehalose 6,6′-dimycolate (TDM), or cord factor, is a crucial stimulus of immune responses during Mycobacterium tuberculosis infection. Although TDM has immuno-stimulatory properties, including adjuvant activity and the ability to induce granuloma formation, the mechanisms underlying these remain unknown. We hypothesized that TDM stimulates transendothelial migration of neutrophils, which are the first immune cells to infiltrate the tissue upon infection. In this study, it was shown that TDM enhances N-formylmethionyl-leucyl-phenylalanine (fMLP)-induced chemotaxis and transendothelial movement by prolonging AKT phosphorylation in human neutrophils. TDM induced expression of macrophage-inducible C-type lectin, a receptor for TDM, and induced secretion of pro-inflammatory cytokines and chemokines in differentiated HL-60 cells. In 2- and 3-D neutrophil migration assays, TDM-stimulated neutrophils showed increased fMLP-induced chemotaxis and transendothelial migration. Interestingly, following fMLP stimulation of TDM-activated neutrophils, AKT, a crucial kinase for neutrophil polarization and chemotaxis, showed prolonged phosphorylation at serine 473. Taken together, these data suggest that TDM modulates transendothelial migration of neutrophils upon mycobacterial infection through prolonged AKT phosphorylation. AKT may therefore be a promising therapeutic target for enhancing immune responses to mycobacterial infection.
AB - Trehalose 6,6′-dimycolate (TDM), or cord factor, is a crucial stimulus of immune responses during Mycobacterium tuberculosis infection. Although TDM has immuno-stimulatory properties, including adjuvant activity and the ability to induce granuloma formation, the mechanisms underlying these remain unknown. We hypothesized that TDM stimulates transendothelial migration of neutrophils, which are the first immune cells to infiltrate the tissue upon infection. In this study, it was shown that TDM enhances N-formylmethionyl-leucyl-phenylalanine (fMLP)-induced chemotaxis and transendothelial movement by prolonging AKT phosphorylation in human neutrophils. TDM induced expression of macrophage-inducible C-type lectin, a receptor for TDM, and induced secretion of pro-inflammatory cytokines and chemokines in differentiated HL-60 cells. In 2- and 3-D neutrophil migration assays, TDM-stimulated neutrophils showed increased fMLP-induced chemotaxis and transendothelial migration. Interestingly, following fMLP stimulation of TDM-activated neutrophils, AKT, a crucial kinase for neutrophil polarization and chemotaxis, showed prolonged phosphorylation at serine 473. Taken together, these data suggest that TDM modulates transendothelial migration of neutrophils upon mycobacterial infection through prolonged AKT phosphorylation. AKT may therefore be a promising therapeutic target for enhancing immune responses to mycobacterial infection.
KW - AKT
KW - migration
KW - neutrophil
KW - trehalose dimycolate
UR - http://www.scopus.com/inward/record.url?scp=85038438246&partnerID=8YFLogxK
U2 - 10.1111/1348-0421.12544
DO - 10.1111/1348-0421.12544
M3 - Article
C2 - 28976590
AN - SCOPUS:85038438246
SN - 0385-5600
VL - 61
SP - 523
EP - 530
JO - Microbiology and Immunology
JF - Microbiology and Immunology
IS - 12
ER -
