Format

Send to

Choose Destination
PLoS Pathog. 2014 Jun 12;10(6):e1004167. doi: 10.1371/journal.ppat.1004167. eCollection 2014 Jun.

The triggering receptor expressed on myeloid cells 2 inhibits complement component 1q effector mechanisms and exerts detrimental effects during pneumococcal pneumonia.

Author information

1
CeMM - Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria; Department of Medicine I, Laboratory of Infection Biology, Medical University of Vienna, Vienna, Austria.
2
Department of Medicine I, Laboratory of Infection Biology, Medical University of Vienna, Vienna, Austria.
3
CeMM - Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria.
4
Department of Pathology, Medical University of Vienna, Vienna, Austria.
5
Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri, United States of America.
6
Department of Clinical Neurosciences, Istituto Nazionale Neurologico Carlo Besta, Milano, Italy.
7
Institute for Medical Microbiology, Immunology and Hygiene, Technical University Munich, Munich, Germany.

Abstract

Phagocytosis and inflammation within the lungs is crucial for host defense during bacterial pneumonia. Triggering receptor expressed on myeloid cells (TREM)-2 was proposed to negatively regulate TLR-mediated responses and enhance phagocytosis by macrophages, but the role of TREM-2 in respiratory tract infections is unknown. Here, we established the presence of TREM-2 on alveolar macrophages (AM) and explored the function of TREM-2 in the innate immune response to pneumococcal infection in vivo. Unexpectedly, we found Trem-2(-/-) AM to display augmented bacterial phagocytosis in vitro and in vivo compared to WT AM. Mechanistically, we detected that in the absence of TREM-2, pulmonary macrophages selectively produced elevated complement component 1q (C1q) levels. We found that these increased C1q levels depended on peroxisome proliferator-activated receptor-δ (PPAR-δ) activity and were responsible for the enhanced phagocytosis of bacteria. Upon infection with S. pneumoniae, Trem-2(-/-) mice exhibited an augmented bacterial clearance from lungs, decreased bacteremia and improved survival compared to their WT counterparts. This work is the first to disclose a role for TREM-2 in clinically relevant respiratory tract infections and demonstrates a previously unknown link between TREM-2 and opsonin production within the lungs.

PMID:
24945405
PMCID:
PMC4055749
DOI:
10.1371/journal.ppat.1004167
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Public Library of Science Icon for PubMed Central
Loading ...
Support Center