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The triggering receptor expressed on myeloid cells 2 inhibits complement component 1q effector mechanisms and exerts detrimental effects during pneumococcal pneumonia
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.
Keywords :
Alveolar/*immunology/metabolism/pathology
Membrane Glycoproteins/genetics/*metabolism
Macrophages
Female
Male
Animals
Mice
Inbred C57BL
Knockout
Apoptosis
Cells
Cultured
Survival Analysis
Phagocytosis
*Disease Models
Animal
Cell Line
Transformed
Complement C1q/genetics/*metabolism
Cytokines/metabolism
Lung/cytology/*immunology/metabolism/pathology
Neutrophil Infiltration
Pneumonia
Pneumococcal/*immunology/metabolism/pathology
PPAR gamma/metabolism
Receptors
Immunologic/genetics/*metabolism
Respiratory Mucosa/cytology/*immunology/metabolism/pathology
https://hal.umontpellier.fr/hal-02168077
Contributeur : Cécile Nowak <>
Soumis le : vendredi 28 juin 2019 - 13:50:46
Dernière modification le : jeudi 30 avril 2020 - 14:22:02
Contributeur : Cécile Nowak <>
Soumis le : vendredi 28 juin 2019 - 13:50:46
Dernière modification le : jeudi 30 avril 2020 - 14:22:02
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