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- Title
The Triggering Receptor Expressed on Myeloid Cells 2 Inhibits Complement Component 1q Effector Mechanisms and Exerts Detrimental Effects during Pneumococcal Pneumonia.
- Authors
Sharif, Omar; Gawish, Riem; Warszawska, Joanna M.; Martins, Rui; Lakovits, Karin; Hladik, Anastasiya; Doninger, Bianca; Brunner, Julia; Korosec, Ana; Schwarzenbacher, Roland E.; Berg, Tiina; Kralovics, Robert; Colinge, Jacques; Mesteri, Ildiko; Gilfillan, Susan; Salmaggi, Andrea; Verschoor, Admar; Colonna, Marco; Knapp, Sylvia
- 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.
- Subjects
PHAGOCYTOSIS; PNEUMOCOCCAL pneumonia; PNEUMONIA; MACROPHAGES; RESPIRATORY infections; ALVEOLAR macrophages
- Publication
PLoS Pathogens, 2014, Vol 10, Issue 6, p1
- ISSN
1553-7366
- Publication type
Article
- DOI
10.1371/journal.ppat.1004167