Journal article
Transepithelial migration of neutrophils into the lung requires TREM-1
The Journal of clinical investigation, Vol.123(1), pp.138-149
01/02/2013
DOI: 10.1172/JCI64181
PMCID: PMC3533287
PMID: 23241959
Abstract
Acute respiratory infections are responsible for more than 4 million deaths each year. Neutrophils play an essential role in the innate immune response to lung infection. These cells have an armamentarium of pattern recognition molecules and antimicrobial agents that identify and eliminate pathogens. In the setting of infection, neutrophil triggering receptor expressed on myeloid cells 1 (TREM-1) amplifies inflammatory signaling. Here we demonstrate for the first time that TREM-1 also plays an important role in transepithelial migration of neutrophils into the airspace. We developed a TREM-1/3–deficient mouse model of pneumonia and found that absence of TREM-1/3 markedly increased mortality following
Pseudomonas aeruginosa
challenge. Unexpectedly, TREM-1/3 deficiency resulted in increased local and systemic cytokine production. TREM-1/3–deficient neutrophils demonstrated intact bacterial killing, phagocytosis, and chemotaxis; however, histologic examination of TREM-1/3–deficient lungs revealed decreased neutrophil infiltration of the airways. TREM-1/3–deficient neutrophils effectively migrated across primary endothelial cell monolayers but failed to migrate across primary airway epithelia grown at the air-liquid interface. These data define a new function for TREM-1 in neutrophil migration across airway epithelial cells and suggest that it amplifies inflammation through targeted neutrophil migration into the lung.
Details
- Title: Subtitle
- Transepithelial migration of neutrophils into the lung requires TREM-1
- Creators
- Julia Klesney-Tait - Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City, Iowa, USAKathy Keck - Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City, Iowa, USAXiaopeng Li - Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City, Iowa, USASusan Gilfillan - Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City, Iowa, USAKarel Otero - Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City, Iowa, USASankar Baruah - Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City, Iowa, USADavid K Meyerholz - Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City, Iowa, USASteven M Varga - Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City, Iowa, USACory J Knudson - Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City, Iowa, USAThomas O Moninger - Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City, Iowa, USAJessica Moreland - Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City, Iowa, USAJoseph Zabner - Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City, Iowa, USAMarco Colonna - Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City, Iowa, USA
- Resource Type
- Journal article
- Publication Details
- The Journal of clinical investigation, Vol.123(1), pp.138-149
- Publisher
- American Society for Clinical Investigation
- DOI
- 10.1172/JCI64181
- PMID
- 23241959
- PMCID
- PMC3533287
- ISSN
- 0021-9738
- eISSN
- 1558-8238
- Language
- English
- Date published
- 01/02/2013
- Academic Unit
- Pulmonary, Critical Care, and Occupational Medicine; Graduate College Admin and Gen; Microbiology and Immunology; Pathology; Internal Medicine
- Record Identifier
- 9984083279302771
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