The TLR4 adaptor TRAM controls the phagocytosis of Gram-negative bacteria by interacting with the Rab11-family interacting protein 2.
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...
| Main Authors: | , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2019-03-01
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| Series: | PLoS Pathogens |
| Online Access: | https://doi.org/10.1371/journal.ppat.1007684 |
| _version_ | 1818901771878137856 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Astrid Skjesol |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-19T20:25:03Z |
| format | Article |
| id | doaj.art-0154430610c447ce88ec48ab14ae47bf |
| institution | Directory Open Access Journal |
| issn | 1553-7366 1553-7374 |
| language | English |
| last_indexed | 2024-12-19T20:25:03Z |
| publishDate | 2019-03-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Pathogens |
| spelling | doaj.art-0154430610c447ce88ec48ab14ae47bf2022-12-21T20:06:51ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742019-03-01153e100768410.1371/journal.ppat.1007684The TLR4 adaptor TRAM controls the phagocytosis of Gram-negative bacteria by interacting with the Rab11-family interacting protein 2.Astrid SkjesolMariia YurchenkoKorbinian BöslCaroline GravastrandKaja Elisabeth NilsenLene Melsæther GrøvdalFederica AglianoFrancesco PataneGermana LentiniHera KimGiuseppe TetiAditya Kumar SharmaRichard K KandasamyBjørnar SporsheimKristian K StarheimDouglas T GolenbockHarald StenmarkMary McCaffreyTerje EspevikHarald HusebyePhagocytosis 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.https://doi.org/10.1371/journal.ppat.1007684 |
| spellingShingle | 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 The TLR4 adaptor TRAM controls the phagocytosis of Gram-negative bacteria by interacting with the Rab11-family interacting protein 2. PLoS Pathogens |
| title | The TLR4 adaptor TRAM controls the phagocytosis of Gram-negative bacteria by interacting with the Rab11-family interacting protein 2. |
| title_full | The TLR4 adaptor TRAM controls the phagocytosis of Gram-negative bacteria by interacting with the Rab11-family interacting protein 2. |
| title_fullStr | The TLR4 adaptor TRAM controls the phagocytosis of Gram-negative bacteria by interacting with the Rab11-family interacting protein 2. |
| title_full_unstemmed | The TLR4 adaptor TRAM controls the phagocytosis of Gram-negative bacteria by interacting with the Rab11-family interacting protein 2. |
| title_short | The TLR4 adaptor TRAM controls the phagocytosis of Gram-negative bacteria by interacting with the Rab11-family interacting protein 2. |
| title_sort | tlr4 adaptor tram controls the phagocytosis of gram negative bacteria by interacting with the rab11 family interacting protein 2 |
| url | https://doi.org/10.1371/journal.ppat.1007684 |
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