TLR4-mediated expulsion of bacteria from infected bladder epithelial cells.
Uropathogenic Escherichia coli invade bladder epithelial cells (BECs) by direct entry into specialized cAMP regulated exocytic compartments. Remarkably, a significant number of these intracellular bacteria are subsequently expelled in a nonlytic and piecemeal fashion by infected BECs. Here, we report that expulsion of intracellular E. coli by infected BECs is initiated by the pattern recognition receptor, Toll-like receptor (TLR)4, after activation by LPS. Also, we reveal that caveolin-1, Rab27b, PKA, and MyRIP are components of the exocytic compartment, and that they form a complex involved in the exocytosis of bacteria. This capacity of TLR4 to mediate the expulsion of intracellular bacteria from infected cells represents a previously unrecognized function for this innate immune receptor.
Song
Jeongmin
J
Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, NC 27710, USA.
Bishop
Brian L
BL
Li
Guojie
G
Grady
Richard
R
Stapleton
Ann
A
Abraham
Soman N
SN
D051242:Caveolin 1 / Q000378:metabolism; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism; D004847:Epithelial Cells / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D004926:Escherichia coli / Q000276:immunology*; D005089:Exocytosis; D006801:Humans; D008070:Lipopolysaccharides / Q000276:immunology; D051197:Toll-Like Receptor 4 / Q000276:immunology* / Q000378:metabolism; D001743:Urinary Bladder / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D033921:Vesicular Transport Proteins / Q000378:metabolism; D020691:rab GTP-Binding Proteins / Q000378:metabolism
D051242:Caveolin 1; D008070:Lipopolysaccharides; C501262:MYRIP protein, human; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4; D033921:Vesicular Transport Proteins; D000242:Cyclic AMP; C512960:Rab27B protein, human; D020691:rab GTP-Binding Proteins
Med Clin North Am. 1991 Mar;75(2):359-73
1996039
Mol Biol Cell. 1999 Apr;10(4):975-86
10198051
Lung. 2000;178(2):91-104
10773135
Proc Natl Acad Sci U S A. 2003 Nov 25;100(24):14012-7
14625374
Traffic. 2004 Mar;5(3):117-28
15086788
Cell Host Microbe. 2007 Jun 14;1(4):287-98
17710226
J Immunol. 1994 Feb 15;152(4):1907-14
8120397
Nat Med. 2007 May;13(5):625-30
17417648
Nat Rev Microbiol. 2008 Feb;6(2):162-8
18157153
J Biol Chem. 2002 Nov 8;277(45):43096-103
12221080
PLoS Pathog. 2007 Apr;3(4):e60
17465679
J Biol Chem. 1989 Oct 5;264(28):16378-82
2674130
J Clin Invest. 1997 Sep 1;100(5):1123-36
9276729
J Biol Chem. 2007 Nov 9;282(45):33155-67
17827149
J Immunol. 2001 Jan 15;166(2):1148-55
11145696
J Bacteriol. 1984 Oct;160(1):61-6
6148338
Infect Immun. 1985 Jun;48(3):625-8
2860067
J Urol. 2007 Jun;177(6):2357-60
17509358
J Biol Chem. 1997 Apr 18;272(16):10353-60
9099672
J Urol. 1994 Aug;152(2 Pt 2):665-70
7517459
Biochemistry. 1998 Aug 4;37(31):11089-96
9693005
Med Clin North Am. 1991 Mar;75(2):495-513
1996046
J Infect Dis. 1999 Oct;180(4):1220-9
10479151
J Neurochem. 1999 Feb;72(2):614-24
9930733
Am J Physiol Renal Physiol. 2005 Aug;289(2):F459-68
15784840
PLoS Med. 2007 Dec;4(12):e329
18092884
J Biol Chem. 2004 Apr 30;279(18):18944-51
14976212
Science. 2003 Jul 4;301(5629):105-7
12843396
Microb Pathog. 1994 Dec;17(6):409-23
7752882
Mol Biol Cell. 2003 Oct;14(10):4103-13
14517322
Curr Opin Microbiol. 2006 Feb;9(1):5-11
16406780