UMMS Affiliation

Program in Innate Immunity, Division of Infectious Diseases and Immunology, Department of Medicine

Publication Date

2019-03-18

Document Type

Article

Disciplines

Amino Acids, Peptides, and Proteins | Bacteria | Hemic and Immune Systems | Immunology and Infectious Disease | Microbiology

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.

Keywords

Phagocytosis, Macrophages, Small interfering RNAs, Staphylococcus aureus, Phagosomes, Immune receptor signaling, Immunoblotting, Toll-like receptors

Rights and Permissions

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

10.1371/journal.ppat.1007684

Source

PLoS Pathog. 2019 Mar 18;15(3):e1007684. doi: 10.1371/journal.ppat.1007684. eCollection 2019 Mar. Link to article on publisher's site

Journal/Book/Conference Title

PLoS pathogens

Comments

Full author list omitted for brevity. For the full list of authors, see article.

Related Resources

Link to Article in PubMed

PubMed ID

30883606

Creative Commons License

Creative Commons Attribution 4.0 License
This work is licensed under a Creative Commons Attribution 4.0 License.

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