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Potentiation of NETs release is novel characteristic of TREM-1 activation and the pharmacological inhibition of TREM-1 could prevent from the deleterious consequences of NETs release in sepsis.

ABSTRACT: During sepsis, neutrophil activation induces endothelial cell (EC) dysfunction partly through neutrophil extracellular trap (NET) release. The triggering receptor expressed on myeloid cell-1 (TREM-1) is an orphan immune receptor that amplifies the inflammatory response mediated by Toll-like receptor-4 (TLR4) engagement. Although the key role of TLR4 signaling in NETosis is known, the role of TREM-1 in this process has not yet been investigated. Here, we report that TREM-1 potentiates NET release by human and murine neutrophils and is a component of the NET structure. In contrast, pharmacologic inhibition or genetic ablation of TREM-1 decreased NETosis in vitro and during experimental septic shock in vivo. Moreover, isolated NETs were able to activate ECs and impair vascular reactivity, and these deleterious effects were dampened by TREM-1 inhibition. TREM-1 may, therefore, constitute a new therapeutic target to prevent NETosis and associated endothelial dysfunction.

SUBMITTER: Boufenzer A

PROVIDER: S-EPMC8026640 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature

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Potentiation of NETs release is novel characteristic of TREM-1 activation and the pharmacological inhibition of TREM-1 could prevent from the deleterious consequences of NETs release in sepsis.

Boufenzer Amir A Carrasco Kevin K Jolly Lucie L Brustolin Benjamin B Di-Pillo Elisa E Derive Marc M Gibot Sébastien S

Cellular & molecular immunology 20210108 2

During sepsis, neutrophil activation induces endothelial cell (EC) dysfunction partly through neutrophil extracellular trap (NET) release. The triggering receptor expressed on myeloid cell-1 (TREM-1) is an orphan immune receptor that amplifies the inflammatory response mediated by Toll-like receptor-4 (TLR4) engagement. Although the key role of TLR4 signaling in NETosis is known, the role of TREM-1 in this process has not yet been investigated. Here, we report that TREM-1 potentiates NET release ...[more]

PMID: 33420354

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Dataset Information

Potentiation of NETs release is novel characteristic of TREM-1 activation and the pharmacological inhibition of TREM-1 could prevent from the deleterious consequences of NETs release in sepsis.

Publications

Potentiation of NETs release is novel characteristic of TREM-1 activation and the pharmacological inhibition of TREM-1 could prevent from the deleterious consequences of NETs release in sepsis.

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