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Triggering receptor expressed on myeloid cells‐1 ( TREM ‐1) improves host defence in pneumococcal pneumonia
Author(s) -
Hommes Tijmen J,
Hoogendijk Arie J,
Dessing Mark C,
van't Veer Cornelis,
Florquin Sandrine,
Colonna Marco,
de Vos Alex F,
van der Poll Tom
Publication year - 2014
Publication title -
the journal of pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.964
H-Index - 184
eISSN - 1096-9896
pISSN - 0022-3417
DOI - 10.1002/path.4361
Subject(s) - streptococcus pneumoniae , pneumococcal pneumonia , immunology , innate immune system , chemokine , bronchoalveolar lavage , immune system , pneumonia , biology , sepsis , myeloid , receptor , pneumococcal infections , microbiology and biotechnology , medicine , lung , antibiotics , biochemistry
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. Copyright © 2014 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.