| First Author | Skjesol A | Year | 2019 |
| Journal | PLoS Pathog | Volume | 15 |
| Issue | 3 | Pages | e1007684 |
| PubMed ID | 30883606 | Mgi Jnum | J:273550 |
| Mgi Id | MGI:6294226 | Doi | 10.1371/journal.ppat.1007684 |
| Citation | Skjesol A, et al. (2019) The TLR4 adaptor TRAM controls the phagocytosis of Gram-negative bacteria by interacting with the Rab11-family interacting protein 2. PLoS Pathog 15(3):e1007684 |
| abstractText | 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. |
