Journal
EUROPEAN JOURNAL OF IMMUNOLOGY
Volume 37, Issue 2, Pages 456-466Publisher
WILEY-BLACKWELL
DOI: 10.1002/eji.200636387
Keywords
innate immunity; rodent; siRNA
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Funding
- MRC [G0500712] Funding Source: UKRI
- Medical Research Council [G0500712] Funding Source: researchfish
- Medical Research Council [G0500712] Funding Source: Medline
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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.
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