2. Academic Validation
  3. The TLR4 adaptor TRAM controls the phagocytosis of Gram-negative bacteria by interacting with the Rab11-family interacting protein 2

The TLR4 adaptor TRAM controls the phagocytosis of Gram-negative bacteria by interacting with the Rab11-family interacting protein 2

  • PLoS Pathog. 2019 Mar 18;15(3):e1007684. doi: 10.1371/journal.ppat.1007684.
Astrid Skjesol 1,  Mariia Yurchenko 1,  Korbinian Bösl 1,  Caroline Gravastrand 1,  Kaja Elisabeth Nilsen 1,  Lene Melsæther Grøvdal 1,  Federica Agliano 1 2,  Francesco Patane 1 2,  Germana Lentini 1 2,  Hera Kim 1,  Giuseppe Teti 2,  Aditya Kumar Sharma 1,  Richard K Kandasamy 1,  Bjørnar Sporsheim 1,  Kristian K Starheim 1,  Douglas T Golenbock 3,  Harald Stenmark 1 4 5,  Mary McCaffrey 6,  Terje Espevik 1 7,  Harald Husebye 1 7
Affiliations

Affiliations

  • 1 Centre of Molecular Inflammation Research, Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway.
  • 2 Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy.
  • 3 Program in Innate Immunity, Division of Infectious Diseases and Immunology, Department of Medicine, University of Massachusetts Medical School, Worcester, MA, United States of America.
  • 4 Centre for Cancer Cell Reprogramming, Faculty of Medicine, University of Oslo, Oslo, Norway.
  • 5 Department for Molecular Cell Biology, Institute for Cancer Research, Oslo University Hospital, Oslo Norway.
  • 6 Molecular Cell Biology Laboratory, Biochemistry Department, Biosciences Institute, University College Cork, Cork, Ireland.
  • 7 The Central Norway Regional Health Authority, St. Olavs Hospital HF, Trondheim, Norway.
PMID: 30883606 DOI: 10.1371/journal.ppat.1007684
Abstract

Phagocytosis is a complex process that eliminates microbes and is performed by specialised cells such as macrophages. Toll-like Receptor 4 (TLR4) is expressed on the surface of macrophages and recognizes Gram-negative bacteria. Moreover, TLR4 has been suggested to play a role in the phagocytosis of Gram-negative bacteria, but the mechanisms remain unclear. Here we have used primary human macrophages and engineered THP-1 monocytes to show that the TLR4 sorting adapter, TRAM, is instrumental for phagocytosis of Escherichia coli as well as Staphylococcus aureus. We find that TRAM forms a complex with Rab11 family interacting protein 2 (FIP2) that is recruited to the phagocytic cups of E. coli. This promotes activation of the actin-regulatory GTPases Rac1 and Cdc42. Our results show that FIP2 guided TRAM recruitment orchestrates actin remodelling and IRF3 activation, two events that are both required for phagocytosis of Gram-negative bacteria.

Figures