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

• DOI: 10.1002/path.4361
• Publication Date: 2014-04-19T10:18:04Z
• 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
• Keywords: Pneumococcal pneumonia; Pneumococcal infections

Streptococcus (S.) pneumoniae is a common Gram-positive pathogen in community-acquired pneumonia and sepsis. Triggering receptor expressed on myeloid cells-1 (TREM-1) phagocytes known to amplify inflammatory responses. Previous studies showed that TREM-1 inhibition protects against lethality during experimental Gram-negative We here aimed investigate the role of an model pneumococcal pneumonia, using TREM-1/3-deficient (Trem-1/3(-/-) ) wild-type (Wt) mice. Additionally ex vivo responsiveness Trem-1/3(-/-) neutrophils macrophages was examined. S. infection resulted rapid recruitment TREM-1-positive into bronchoalveolar space, while high constitutive expression alveolar remained unchanged. TREM-1/3 deficiency led increased lethality, accompanied by enhanced growth at primary site dissemination distant organs. Within first 3-6 h infection, mice demonstrated strongly impaired innate immune response airways, as reflected reduced local release cytokines chemokines delayed influx neutrophils. produced fewer upon exposure vitro were less capable phagocytosing this pathogen. did not influence neutrophil pneumoniae. These results identify key player protective immunity most likely enhancing early macrophages.