title: Triggering receptor expressed on myeloid cells-1 (TREM-1) modulates immune responses to Aspergillus fumigatus during fungal asthma in mice.
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.
authors: Immunology Program, Department of Pathology, University of Michigan Medical School, 109 Zina Pitcher Place, Ann Arbor, MI 48109-2200, USA.
authors: Karen F
authors: KF
authors: Buckland
authors: Hemanth
authors: H
authors: Ramaprakash
authors: Lynne A
authors: LA
authors: Murray
authors: Kristin J
authors: KJ
authors: Carpenter
authors: Esther S
authors: ES
authors: Choi
authors: Steven L
authors: SL
authors: Kunkel
authors: Nicholas W
authors: NW
authors: Lukacs
authors: Zhou
authors: Z
authors: Xing
authors: Naoko
authors: N
authors: Aoki
authors: Dominik
authors: D
authors: Hartl
authors: Cory M
authors: CM
authors: Hogaboam
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