Program in Innate Immunity, Division of Infectious Diseases and Immunology, Department of Medicine
Amino Acids, Peptides, and Proteins | Bacteria | Hemic and Immune Systems | Immunology and Infectious Disease | Microbiology
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.
Phagocytosis, Macrophages, Small interfering RNAs, Staphylococcus aureus, Phagosomes, Immune receptor signaling, Immunoblotting, Toll-like receptors
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Copyright: © 2019 Skjesol et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
DOI of Published Version
PLoS Pathog. 2019 Mar 18;15(3):e1007684. doi: 10.1371/journal.ppat.1007684. eCollection 2019 Mar. Link to article on publisher's site
Skjesol, Astrid; Golenbock, Douglas T.; and Husebye, Harald, "The TLR4 adaptor TRAM controls the phagocytosis of Gram-negative bacteria by interacting with the Rab11-family interacting protein 2" (2019). Open Access Articles. 3812.
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This work is licensed under a Creative Commons Attribution 4.0 License.