Mycobacterial cord factor enhances migration of neutrophil-like HL-60 cells by prolonging AKT phosphorylation

Wook Bin Lee, Ji Jing Yan, Ji Seon Kang, Seok Chung, Lark Kyun Kim

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
Pages (from-to)523-530
Number of pages8
JournalMicrobiology and Immunology
Volume61
Issue number12
DOIs
Publication statusPublished - 2017 Dec 1

Keywords

  • AKT
  • migration
  • neutrophil
  • trehalose dimycolate

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Virology

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