| Added by | mollevi |
|---|---|
| Last modified by | jacques.colinge |
| Group name | EquipeJC |
| Item Type | Journal Article |
| Title | The triggering receptor expressed on myeloid cells 2 inhibits complement component 1q effector mechanisms and exerts detrimental effects during pneumococcal pneumonia |
| Creator | Sharif et al. |
| Author | O. Sharif |
| Author | R. Gawish |
| Author | J. M. Warszawska |
| Author | R. Martins |
| Author | K. Lakovits |
| Author | A. Hladik |
| Author | B. Doninger |
| Author | J. Brunner |
| Author | A. Korosec |
| Author | R. E. Schwarzenbacher |
| Author | T. Berg |
| Author | R. Kralovics |
| Author | J. Colinge |
| Author | I. Mesteri |
| Author | S. Gilfillan |
| Author | A. Salmaggi |
| Author | A. Verschoor |
| Author | M. Colonna |
| Author | S. Knapp |
| 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-delta (PPAR-delta) 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. |
| Publication | PLoS Pathog |
| Volume | 10 |
| Pages | e1004167 |
| Date | Jun 2014 |
| Journal Abbr | PLoS pathogens |
| DOI | 10.1371/journal.ppat.1004167 |
| ISSN | 1553-7374 (Electronic) 1553-7366 (Linking) |
| Tags | *Disease Models, Animal, Animals, Apoptosis, Cell Line, Transformed, Cells, Cultured, Complement C1q/genetics/*metabolism, Cytokines/metabolism, Female, Lung/cytology/*immunology/metabolism/pathology, Macrophages, Alveolar/*immunology/metabolism/pathology, Male, Membrane Glycoproteins/genetics/*metabolism, Mice, Inbred C57BL, Mice, Knockout, Neutrophil Infiltration, original, Phagocytosis, Pneumonia, Pneumococcal/*immunology/metabolism/pathology, PPAR gamma/metabolism, Receptors, Immunologic/genetics/*metabolism, Respiratory Mucosa/cytology/*immunology/metabolism/pathology, Survival Analysis |
| Date Added | 2018/11/14 - 11:48:35 |
| Date Modified | 2019/05/14 - 20:58:31 |
| Notes and Attachments | (Note) (Note) 24945405 (Attachment) |
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