Triggering receptor expressed on myeloid cells-1 (TREM-1) improves host defence in pneumococcal pneumonia.
Streptococcus (S.) pneumoniae is a common Gram-positive pathogen in community-acquired pneumonia and sepsis. Triggering receptor expressed on myeloid cells-1 (TREM-1) is a receptor on phagocytes known to amplify inflammatory responses. Previous studies showed that TREM-1 inhibition protects against lethality during experimental Gram-negative sepsis. We here aimed to investigate the role of TREM-1 in an experimental model of pneumococcal pneumonia, using TREM-1/3-deficient (Trem-1/3(-/-) ) and wild-type (Wt) mice. Additionally ex vivo responsiveness of Trem-1/3(-/-) neutrophils and macrophages was examined. S. pneumoniae infection resulted in a rapid recruitment of TREM-1-positive neutrophils into the bronchoalveolar space, while high constitutive TREM-1 expression on alveolar macrophages remained unchanged. TREM-1/3 deficiency led to increased lethality, accompanied by enhanced growth of S. pneumoniae at the primary site of infection and increased dissemination to distant organs. Within the first 3-6 h of infection, Trem-1/3(-/-) mice demonstrated a strongly impaired innate immune response in the airways, as reflected by reduced local release of cytokines and chemokines and a delayed influx of neutrophils. Trem-1/3(-/-) alveolar macrophages produced fewer cytokines upon exposure to S. pneumoniae in vitro and were less capable of phagocytosing this pathogen. TREM-1/3 deficiency did not influence neutrophil responsiveness to S. pneumoniae. These results identify TREM-1 as a key player in protective innate immunity during pneumococcal pneumonia, most likely by enhancing the early immune response of alveolar macrophages.
['Hommes|Tijmen J|TJ|', 'Hoogendijk|Arie J|AJ|', 'Dessing|Mark C|MC|', "Van't Veer|Cornelis|C|", 'Florquin|Sandrine|S|', 'Colonna|Marco|M|', 'de Vos|Alex F|AF|', 'van der Poll|Tom|T|']
D000818:Animals D002465:Cell Movement D016207:Cytokines D004195:Disease Models, Animal D007113:Immunity, Innate D016676:Macrophages, Alveolar D008297:Male D008562:Membrane Glycoproteins D051379:Mice D008810:Mice, Inbred C57BL D018345:Mice, Knockout D009504:Neutrophils D011018:Pneumonia, Pneumococcal D011971:Receptors, Immunologic D013296:Streptococcus pneumoniae D000073871:Triggering Receptor Expressed on Myeloid Cells-1
TREM-1 pneumococcal pneumonia macrophages innate immunity phagocytosis