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 pathogens (2019-03-19)

Astrid Skjesol, Mariia Yurchenko, Korbinian Bösl, Caroline Gravastrand, Kaja Elisabeth Nilsen, Lene Melsæther Grøvdal, Federica Agliano, Francesco Patane, Germana Lentini, Hera Kim, Giuseppe Teti, Aditya Kumar Sharma, Richard K Kandasamy, Bjørnar Sporsheim, Kristian K Starheim, Douglas T Golenbock, Harald Stenmark, Mary McCaffrey, Terje Espevik, Harald Husebye

PMID30883606

摘要

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.