Triggering receptor expressed on myeloid cells-1 (TREM-1) improves host defence in pneumococcal pneumonia

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

Research output: Contribution to journalArticlepeer-review

39 Scopus citations

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.

Original languageEnglish
Pages (from-to)357-367
Number of pages11
JournalJournal of Pathology
Volume233
Issue number4
DOIs
StatePublished - Aug 2014

Keywords

  • TREM-1
  • innate immunity
  • macrophages
  • phagocytosis
  • pneumococcal pneumonia

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