title: Soluble TREM-like transcript-1 regulates leukocyte activation and controls microbial sepsis.
abstract: The triggering receptor expressed on myeloid cells (TREM)-1 plays a crucial role during the onset of sepsis by amplifying the host immune response. The TREM-like transcript-1 (TLT-1) belongs to the TREM family, is selectively expressed on activated platelets, and is known to facilitate platelet aggregation through binding to fibrinogen. In this study, we show that a soluble form of TLT-1 is implicated in the regulation of inflammation during sepsis by dampening leukocyte activation and modulating platelet-neutrophil crosstalk. A 17-aa sequence of the TLT-1 extracellular domain (LR17) is responsible for this activity through competition with the TREM-1 ligand. Whereas early or late LR17 treatment of septic mice improves survival, treml-1(-/-) animals are highly susceptible to polymicrobial infection. The present findings identify platelet-derived soluble TLT-1 as a potent endogenous regulator of sepsis-associated inflammation and open new therapeutic perspectives. We anticipate soluble TLT-1 to be important in regulating leukocyte activation during other noninfectious inflammatory disorders.
authors.affiliation: Groupe Choc, Contrat Avenir INSERM, Faculté de Médecine, Nancy Université, 54000 Nancy, France.
authors.forename: Marc
authors.initials: M
authors.lastname: Derive
authors.forename: Youcef
authors.initials: Y
authors.lastname: Bouazza
authors.forename: Nacira
authors.initials: N
authors.lastname: Sennoun
authors.forename: Sandra
authors.initials: S
authors.lastname: Marchionni
authors.forename: Laura
authors.initials: L
authors.lastname: Quigley
authors.forename: Valance
authors.initials: V
authors.lastname: Washington
authors.forename: Frédéric
authors.initials: F
authors.lastname: Massin
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Max
authors.forename: Jill
authors.initials: J
authors.lastname: Ford
authors.forename: Corentine
authors.initials: C
authors.lastname: Alauzet
authors.forename: Bruno
authors.initials: B
authors.lastname: Levy
authors.forename: Daniel W
authors.initials: DW
authors.lastname: McVicar
authors.forename: Sébastien
authors.initials: S
authors.lastname: Gibot
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001792:Blood Platelets / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology*; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D009000:Monocytes / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D018375:Neutrophil Activation / Q000276:immunology; D011897:Random Allocation; D011971:Receptors, Immunologic / Q000097:blood / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D018805:Sepsis / Q000097:blood / Q000276:immunology* / Q000382:microbiology*
chemical_list: D011971:Receptors, Immunologic; C473366:TREML1 protein, human; C471763:Treml1 protein, mouse