Title |
Triggering receptor expressed on myeloid cells‐1 (TREM‐1) improves host defence in pneumococcal pneumonia
|
---|---|
Published in |
The Journal of Pathology, June 2014
|
DOI | 10.1002/path.4361 |
Pubmed ID | |
Authors |
Tijmen J Hommes, Arie J Hoogendijk, Mark C Dessing, Cornelis van't Veer, Sandrine Florquin, Marco Colonna, Alex F de Vos, Tom van der Poll |
Abstract |
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. |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
United Kingdom | 1 | 5% |
United States | 1 | 5% |
Brazil | 1 | 5% |
Unknown | 19 | 86% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Student > Ph. D. Student | 5 | 23% |
Researcher | 4 | 18% |
Student > Bachelor | 2 | 9% |
Student > Doctoral Student | 2 | 9% |
Student > Master | 2 | 9% |
Other | 1 | 5% |
Unknown | 6 | 27% |
Readers by discipline | Count | As % |
---|---|---|
Agricultural and Biological Sciences | 6 | 27% |
Medicine and Dentistry | 5 | 23% |
Immunology and Microbiology | 3 | 14% |
Biochemistry, Genetics and Molecular Biology | 1 | 5% |
Unspecified | 1 | 5% |
Other | 0 | 0% |
Unknown | 6 | 27% |