TREM-1 deficiency can attenuate disease severity without affecting pathogen clearance.

Détails

Ressource 1Télécharger: BIB_221705A3B161.P001.pdf (3350.20 [Ko])
Etat: Public
Version: de l'auteur
ID Serval
serval:BIB_221705A3B161
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
TREM-1 deficiency can attenuate disease severity without affecting pathogen clearance.
Périodique
PLoS Pathogens
Auteur(s)
Weber B., Schuster S., Zysset D., Rihs S., Dickgreber N., Schürch C., Riether C., Siegrist M., Schneider C., Pawelski H., Gurzeler U., Ziltener P., Genitsch V., Tacchini-Cottier F., Ochsenbein A., Hofstetter W., Kopf M., Kaufmann T., Oxenius A., Reith W., Saurer L., Mueller C.
ISSN
1553-7374 (Electronic)
ISSN-L
1553-7366
Statut éditorial
Publié
Date de publication
2014
Volume
10
Numéro
1
Pages
e1003900
Langue
anglais
Résumé
Triggering receptor expressed on myeloid cells-1 (TREM-1) is a potent amplifier of pro-inflammatory innate immune reactions. While TREM-1-amplified responses likely aid an improved detection and elimination of pathogens, excessive production of cytokines and oxygen radicals can also severely harm the host. Studies addressing the pathogenic role of TREM-1 during endotoxin-induced shock or microbial sepsis have so far mostly relied on the administration of TREM-1 fusion proteins or peptides representing part of the extracellular domain of TREM-1. However, binding of these agents to the yet unidentified TREM-1 ligand could also impact signaling through alternative receptors. More importantly, controversial results have been obtained regarding the requirement of TREM-1 for microbial control. To unambiguously investigate the role of TREM-1 in homeostasis and disease, we have generated mice deficient in Trem1. Trem1(-/-) mice are viable, fertile and show no altered hematopoietic compartment. In CD4(+) T cell- and dextran sodium sulfate-induced models of colitis, Trem1(-/-) mice displayed significantly attenuated disease that was associated with reduced inflammatory infiltrates and diminished expression of pro-inflammatory cytokines. Trem1(-/-) mice also exhibited reduced neutrophilic infiltration and decreased lesion size upon infection with Leishmania major. Furthermore, reduced morbidity was observed for influenza virus-infected Trem1(-/-) mice. Importantly, while immune-associated pathologies were significantly reduced, Trem1(-/-) mice were equally capable of controlling infections with L. major, influenza virus, but also Legionella pneumophila as Trem1(+/+) controls. Our results not only demonstrate an unanticipated pathogenic impact of TREM-1 during a viral and parasitic infection, but also indicate that therapeutic blocking of TREM-1 in distinct inflammatory disorders holds considerable promise by blunting excessive inflammation while preserving the capacity for microbial control.
Pubmed
Web of science
Open Access
Oui
Création de la notice
01/05/2014 13:44
Dernière modification de la notice
20/08/2019 13:59
Données d'usage