• Tijmen J Hommes, Arie J Hoogendijk, Mark C Dessing, Cornelis Van't Veer, Sandrine Florquin, Marco Colonna, Alex F de Vos, and Tom van der Poll.
• Center for Experimental and Molecular Medicine, Academic Medical Centre, University of Amsterdam, The Netherlands; Centre for Infection and Immunity, Academic Medical Centre, University of Amsterdam, The Netherlands.
• J. Pathol. 2014 Aug 1;233(4):357-67.

AbstractStreptococcus (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.

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