The TLR4 adaptor TRAM controls the phagocytosis of Gram-negative bacteria by interacting with the Rab11-family interacting protein 2.
Adaptor Proteins, Signal Transducing
/ metabolism
Animals
Carrier Proteins
/ metabolism
Endocytosis
Endosomes
Escherichia coli
/ pathogenicity
HEK293 Cells
Humans
Interferon Regulatory Factor-3
Lipopolysaccharides
Macrophages
/ immunology
Membrane Proteins
/ metabolism
Mice
Mice, Inbred C57BL
Myeloid Differentiation Factor 88
Phagocytosis
/ physiology
Primary Cell Culture
Protein Transport
Signal Transduction
Staphylococcus aureus
/ pathogenicity
THP-1 Cells
Toll-Like Receptor 4
/ metabolism
cdc42 GTP-Binding Protein
rab GTP-Binding Proteins
rac1 GTP-Binding Protein
Journal
PLoS pathogens
ISSN: 1553-7374
Titre abrégé: PLoS Pathog
Pays: United States
ID NLM: 101238921
Informations de publication
Date de publication:
03 2019
03 2019
Historique:
received:
04
06
2018
accepted:
07
03
2019
revised:
28
03
2019
pubmed:
19
3
2019
medline:
12
4
2019
entrez:
19
3
2019
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 30883606
doi: 10.1371/journal.ppat.1007684
pii: PPATHOGENS-D-18-01130
pmc: PMC6438586
doi:
Substances chimiques
Adaptor Proteins, Signal Transducing
0
Carrier Proteins
0
IRF3 protein, human
0
Interferon Regulatory Factor-3
0
Lipopolysaccharides
0
Membrane Proteins
0
Myeloid Differentiation Factor 88
0
RAC1 protein, human
0
TICAM2 protein, human
0
TLR4 protein, human
0
Toll-Like Receptor 4
0
CDC42 protein, human
EC 3.6.5.2
RAB11FIP2 protein, human
EC 3.6.5.2
cdc42 GTP-Binding Protein
EC 3.6.5.2
rab GTP-Binding Proteins
EC 3.6.5.2
rac1 GTP-Binding Protein
EC 3.6.5.2
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e1007684Déclaration de conflit d'intérêts
The authors have declared that no competing interests exist.
Références
J Biol Chem. 1999 May 7;274(19):13198-204
pubmed: 10224076
Philos Trans R Soc Lond B Biol Sci. 2000 Jul 29;355(1399):965-70
pubmed: 11128990
Nat Rev Mol Cell Biol. 2001 Feb;2(2):107-17
pubmed: 11252952
Nucleic Acids Res. 2001 May 1;29(9):e45
pubmed: 11328886
J Biol Chem. 2001 Oct 19;276(42):39067-75
pubmed: 11495908
J Biol Chem. 2001 Dec 7;276(49):45856-61
pubmed: 11585836
Semin Immunol. 2001 Dec;13(6):347-55
pubmed: 11708890
J Biol Chem. 2002 Dec 20;277(51):49158-66
pubmed: 12364336
Curr Top Microbiol Immunol. 2002;270:121-44
pubmed: 12467248
J Exp Med. 2003 Oct 6;198(7):1043-55
pubmed: 14517278
Mol Biol Cell. 2004 May;15(5):2456-69
pubmed: 15004234
Science. 2004 May 14;304(5673):1014-8
pubmed: 15143282
J Cell Sci. 2004 Sep 1;117(Pt 19):4365-75
pubmed: 15304524
Immunity. 2005 Oct;23(4):409-17
pubmed: 16226506
Mol Biol Cell. 2006 Jan;17(1):163-77
pubmed: 16251358
Cell. 2006 Jun 2;125(5):943-55
pubmed: 16751103
Structure. 2006 Aug;14(8):1273-83
pubmed: 16905101
Traffic. 2007 Mar;8(3):241-50
pubmed: 17319801
Inflamm Res. 2007 Jan;56(1):45-50
pubmed: 17334670
Nat Rev Immunol. 2007 May;7(5):353-64
pubmed: 17457343
Nat Immunol. 2008 Apr;9(4):361-8
pubmed: 18297073
J Mol Biol. 2008 May 30;379(2):251-60
pubmed: 18440553
Cell Res. 2008 Jul;18(7):745-55
pubmed: 18542102
Nat Immunol. 2009 Jun;10(6):579-86
pubmed: 19412184
J Biol Chem. 2009 Aug 14;284(33):22481-90
pubmed: 19542231
PLoS One. 2009 Aug 06;4(8):e6529
pubmed: 19657394
Nat Rev Mol Cell Biol. 2009 Sep;10(9):597-608
pubmed: 19696797
Biochem Soc Trans. 2009 Oct;37(Pt 5):1032-6
pubmed: 19754446
Mol Cell. 2009 Sep 24;35(6):841-55
pubmed: 19782033
Immunity. 2010 Oct 29;33(4):583-96
pubmed: 20933442
J Cell Sci. 2010 Dec 1;123(Pt 23):4011-8
pubmed: 21084561
Blood. 2011 Oct 13;118(15):4199-208
pubmed: 21846901
OMICS. 2012 May;16(5):284-7
pubmed: 22455463
Proc Natl Acad Sci U S A. 2013 Dec 3;110(49):19908-13
pubmed: 24255114
Traffic. 2014 Mar;15(3):292-308
pubmed: 24372966
Mol Biol Cell. 2014 Nov 1;25(21):3330-41
pubmed: 25165138
Immunol Rev. 2014 Nov;262(1):193-215
pubmed: 25319336
J Immunol. 2014 Dec 15;193(12):6090-102
pubmed: 25385819
J Biol Chem. 2015 Feb 6;290(6):3209-22
pubmed: 25505250
Nucleic Acids Res. 2015 Apr 20;43(7):e47
pubmed: 25605792
Nat Methods. 2015 Feb;12(2):115-21
pubmed: 25633503
Traffic. 2015 Jul;16(7):677-90
pubmed: 25707286
Nature. 2015 Apr 9;520(7546):234-8
pubmed: 25855459
J Immunol. 2015 Nov 1;195(9):4456-65
pubmed: 26408662
Int J Cancer. 2016 Apr 1;138(7):1680-8
pubmed: 26502090
Biochem J. 2017 Mar 15;474(7):1163-1174
pubmed: 28159912
Trends Immunol. 2017 Jun;38(6):407-422
pubmed: 28416446
PLoS Pathog. 2017 Aug 7;13(8):e1006556
pubmed: 28787457
J Cell Biol. 2018 Apr 2;217(4):1411-1429
pubmed: 29440514
Sci Rep. 2018 Aug 29;8(1):12998
pubmed: 30158654
Rev Infect Dis. 1988 Jan-Feb;10(1):223-7
pubmed: 3281221
Science. 1998 Nov 27;282(5394):1717-21
pubmed: 9831565
Science. 1998 Dec 11;282(5396):2085-8
pubmed: 9851930