RGD Reference Report - TREM-1 deficiency can attenuate disease severity without affecting pathogen clearance. - Rat Genome Database

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

Authors: Weber, Benjamin  Schuster, Steffen  Zysset, Daniel  Rihs, Silvia  Dickgreber, Nina  Schürch, Christian  Riether, Carsten  Siegrist, Mark  Schneider, Christoph  Pawelski, Helga  Gurzeler, Ursina  Ziltener, Pascal  Genitsch, Vera  Tacchini-Cottier, Fabienne  Ochsenbein, Adrian  Hofstetter, Willy  Kopf, Manfred  Kaufmann, Thomas  Oxenius, Annette  Reith, Walter  Saurer, Leslie  Mueller, Christoph 
Citation: Weber B, etal., PLoS Pathog. 2014 Jan;10(1):e1003900. doi: 10.1371/journal.ppat.1003900. Epub 2014 Jan 16.
RGD ID: 126925972
Pubmed: PMID:24453980   (View Abstract at PubMed)
PMCID: PMC3894224   (View Article at PubMed Central)
DOI: DOI:10.1371/journal.ppat.1003900   (Journal Full-text)

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.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
TREM1Humancolitis severityISOTrem1 (Mus musculus) RGD 
Trem1Ratcolitis severityISOTrem1 (Mus musculus) RGD 
Trem1Mousecolitis severityIMP  RGD 
TREM1Humanleishmaniasis severityISOTrem1 (Mus musculus) RGD 
Trem1Ratleishmaniasis severityISOTrem1 (Mus musculus) RGD 
Trem1Mouseleishmaniasis severityIMP  RGD 
TREM1Humanswine influenza severityISOTrem1 (Mus musculus) RGD 
Trem1Ratswine influenza severityISOTrem1 (Mus musculus) RGD 
Trem1Mouseswine influenza severityIMP  RGD 

Objects Annotated

Genes (Rattus norvegicus)
Trem1  (triggering receptor expressed on myeloid cells 1)

Genes (Mus musculus)
Trem1  (triggering receptor expressed on myeloid cells 1)

Genes (Homo sapiens)
TREM1  (triggering receptor expressed on myeloid cells 1)


Additional Information