Transepithelial migration of neutrophils into the lung requires TREM-1

Julia Klesney-Tait, Kathy Keck, Xiaopeng Li, Susan Gilfillan, Karel Otero, Sankar Baruah, David K. Meyerholz, Steven M. Varga, Cory J. Knudson, Thomas O. Moninger, Jessica Moreland, Joseph Zabner, Marco Colonna

Research output: Contribution to journalArticle

85 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)138-149
Number of pages12
JournalJournal of Clinical Investigation
Volume123
Issue number1
DOIs
StatePublished - Jan 2 2013

ASJC Scopus subject areas

  • Medicine(all)

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    Klesney-Tait, J., Keck, K., Li, X., Gilfillan, S., Otero, K., Baruah, S., Meyerholz, D. K., Varga, S. M., Knudson, C. J., Moninger, T. O., Moreland, J., Zabner, J., & Colonna, M. (2013). Transepithelial migration of neutrophils into the lung requires TREM-1. Journal of Clinical Investigation, 123(1), 138-149. https://doi.org/10.1172/JCI64181