title: Plasma Membrane Profiling Reveals Upregulation of ABCA1 by Infected Macrophages Leading to Restriction of Mycobacterial Growth.
abstract: The plasma membrane represents a critical interface between the internal and extracellular environments, and harbors multiple proteins key receptors and transporters that play important roles in restriction of intracellular infection. We applied plasma membrane profiling, a technique that combines quantitative mass spectrometry with selective cell surface aminooxy-biotinylation, to Bacille Calmette-Guérin (BCG)-infected THP-1 macrophages. We quantified 559 PM proteins in BCG-infected THP-1 cells. One significantly upregulated cell-surface protein was the cholesterol transporter ABCA1. We showed that ABCA1 was upregulated on the macrophage cell-surface following infection with pathogenic mycobacteria and knockdown of ABCA1 resulted in increased mycobacterial survival within macrophages, suggesting that it may be a novel mycobacterial host-restriction factor.
authors.affiliation: Collaboration Innovation Centre for the Diagnosis and Treatment of Infectious Diseases, School of Medicine, Tsinghua University Beijing, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Long
authors.affiliation: Harvard TH Chan School of Public Health, Boston MA, USA.
authors.forename: Robindra
authors.initials: R
authors.lastname: Basu Roy
authors.affiliation: Harvard TH Chan School of Public Health, Boston MA, USA.
authors.forename: Yanjia J
authors.initials: YJ
authors.lastname: Zhang
authors.affiliation: Cambridge Institute for Medical Research, University of Cambridge Cambridge, UK.
authors.forename: Robin
authors.initials: R
authors.lastname: Antrobus
authors.affiliation: Collaboration Innovation Centre for the Diagnosis and Treatment of Infectious Diseases, School of Medicine, Tsinghua University Beijing, China.
authors.forename: Yuxian
authors.initials: Y
authors.lastname: Du
authors.affiliation: Cancer Research UK Manchester Institute, University of Manchester Manchester, UK.
authors.forename: Duncan L
authors.initials: DL
authors.lastname: Smith
authors.affiliation: Cambridge Institute for Medical Research, University of Cambridge Cambridge, UK.
authors.forename: Michael P
authors.initials: MP
authors.lastname: Weekes
authors.affiliation: Collaboration Innovation Centre for the Diagnosis and Treatment of Infectious Diseases, School of Medicine, Tsinghua UniversityBeijing, China; Harvard TH Chan School of Public Health, BostonMA, USA.
authors.forename: Babak
authors.initials: B
authors.lastname: Javid
keywords: ABCA1; Mycobacterium; SILAC; cholesterol; plasma membrane profiling