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Triggering Receptor Expressed on Myeloid cells-1 (TREM-1) Modulates Immune Responses to Aspergillus fumigatus During Fungal Asthma in Mice

Buckland, KF; Ramaprakash, H; Murray, LA; Carpenter, KJ; Choi, ES; Kunkel, SL; Lukacs, NW; ... Hogaboam, CM; + view all (2011) Triggering Receptor Expressed on Myeloid cells-1 (TREM-1) Modulates Immune Responses to Aspergillus fumigatus During Fungal Asthma in Mice. IMMUNOL INVEST , 40 (7-8) 692 - 722. 10.3109/08820139.2011.578270.

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Abstract

Triggering receptor expressed on myeloid cells-1 (TREM-1) expression is increased during pulmonary fungal infection suggesting that this receptor might be involved in anti-fungal immune responses. To address the role of TREM-1 in a murine model of fungal allergic airway disease, A. fumigatus-sensitized CBA/J mice received by intratracheal injection a mixture of live A. fumigatus conidia and one of a control adenovirus vector (Ad70), an adenovirus containing a gene encoding for the extracellular domain of mouse TREM-1 and the F-c portion of human IgG (AdTREM-1Ig; a soluble inhibitor of TREM-1 function), or an adenovirus containing mouse DAP12 (AdDAP12; DAP12 is an intracellular adaptor protein required for TREM-1 signaling), and examined at various days after challenge. Whole lung TREM-1 levels peaked at day 3 whereas circulating TREM-1 levels peaked at day 30 in this fungal asthma model. AdTREM-1Ig-treated mice exhibited significantly higher airway hyperresponsiveness following methacholine challenge compared with Ad70- and AdDAP12-treated mice. Whole lung analysis of AdTREM-1Ig treated mice revealed markedly higher amounts of fungal material compared with the other groups. ELISA analysis of whole lung and bronchoalveolar lavage samples indicated that several pro-allergic cytokine and chemokines including CCL17 and CCL22 were significantly increased in the AdTREM-1Ig group compared with the other groups. Finally, Pam3Cys and soluble Aspergillus antigens induced TREM-1 transcript expression in macrophages in a TLR2 dependent manner. In conclusion, TREM-1 modulates the immune response directed against A. fumigatus during experimental fungal asthma.

Type: Article
Title: Triggering Receptor Expressed on Myeloid cells-1 (TREM-1) Modulates Immune Responses to Aspergillus fumigatus During Fungal Asthma in Mice
DOI: 10.3109/08820139.2011.578270
Keywords: Allergic Inflammation, Fungus, TREM-1, ALLERGIC BRONCHOPULMONARY ASPERGILLOSIS, INFLAMMATORY RESPONSES, INVASIVE ASPERGILLOSIS, CYSTIC-FIBROSIS, KNOCKOUT MICE, AIRWAY HYPERRESPONSIVENESS, PERIBRONCHIAL FIBROSIS, CYTOKINE PRODUCTION, MOLECULAR METHODS, MURINE MODEL
UCL classification: UCL > School of Life and Medical Sciences
UCL > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Child Health
URI: http://discovery.ucl.ac.uk/id/eprint/1307777
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