TREM-1 promotes survival during septic shock in mice.
Triggering receptor expressed on myeloid (TREM)-1 is integral to the inflammatory response occurring during septic shock, although its precise function has yet to be determined. Here we show that in vivo silencing of TREM-1 using siRNA duplexes in a fecal peritonitis mouse model resulted in a blunted inflammatory response and increased mortality. This was associated with impaired bacterial clearance related to marked inhibition of the neutrophil oxidative burst. By contrast, TREM-1-silenced mice were highly resistant to a lethal endotoxin challenge, while partial silencing of TREM-1 in the bacterial peritonitis model produced a significant survival benefit. These data highlight the crucial role of the TREM-1 pathway in mounting an adequate inflammatory and cytotoxic response to polymicrobial sepsis, and both the therapeutic promise and potential risks of its modulation.
Gibot
Sébastien
S
Réanimation Médicale, Hôpital Central, Nancy, France. s.gibot@chu-nancy.fr
Massin
Frederic
F
Marcou
Markella
M
Taylor
Valerie
V
Stidwill
Ray
R
Wilson
Peter
P
Singer
Mervyn
M
Bellingan
Geoff
G
D000818:Animals; D019446:Endotoxemia / Q000276:immunology / Q000503:physiopathology; D005434:Flow Cytometry; D007249:Inflammation / Q000276:immunology / Q000378:metabolism*; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D010538:Peritonitis / Q000150:complications / Q000276:immunology; D034741:RNA, Small Interfering; D011971:Receptors, Immunologic / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012772:Shock, Septic / Q000209:etiology / Q000276:immunology / Q000401:mortality* / Q000503:physiopathology*; D000073871:Triggering Receptor Expressed on Myeloid Cells-1
D008562:Membrane Glycoproteins; D034741:RNA, Small Interfering; D011971:Receptors, Immunologic; C517262:TREM1 protein, mouse; D000073871:Triggering Receptor Expressed on Myeloid Cells-1