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The beta-glucan receptor dectin-1 recognizes specific morphologies of aspergillus fumigatus

Steele, C and Rapaka, RR and Metz, A and Pop, SM and Williams, DL and Gordon, S and Kolls, JK and Brown, GD (2005) The beta-glucan receptor dectin-1 recognizes specific morphologies of aspergillus fumigatus. PLoS Pathogens, 1 (4). 0323 - 0334. ISSN 1553-7366

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Abstract

Alveolar macrophages represent a first-line innate host defense mechanism for clearing inhaled Aspergillus fumigatus from the lungs, yet contradictory data exist as to which alveolar macrophage recognition receptor is critical for innate immunity to A. fumigatus. Acknowledging that the A. fumigatus cell wall contains a high beta-1,3-glucan content, we questioned whether the beta-glucan receptor dectin-1 played a role in this recognition process. Monoclonal antibody, soluble receptor, and competitive carbohydrate blockage indicated that the alveolar macrophage inflammatory response, specifically the production of tumor necrosis factor-α (TNF-α), interleukin-1α (IL-1α), IL-1β, IL-6, CXCL2/macrophage inflammatory protein-2 (MIP-2), CCL3/macrophage inflammatory protein-1α (MIP-1α), granulocyte-colony stimulating factor (G-CSF), and granulocyte monocyte-CSF (GM-CSF), to live A. fumigatus was dependent on recognition via the beta-glucan receptor dectin-1. The inflammatory response was triggered at the highest level by A. fumigatus swollen conidia and early germlings and correlated to the levels of surface-exposed beta glucans, indicating that dectin-1 preferentially recognizes specific morphological forms of A. fumigatus. Intratracheal administration of A. fumigatus conidia to mice in the presence of a soluble dectin-Fc fusion protein reduced both lung proinflammatory cytokine/chemokine levels and cellular recruitment while modestly increasing the A. fumigatus fungal burden, illustrating the importance of beta-glucan-initiated dectin-1 signaling in defense against this pathogen. Collectively, these data show that dectin-1 is centrally required for the generation of alveolar macrophage proinflammatory responses to A. fumigatus and to our knowledge provides the first in vivo evidence for the role of dectin-1 in fungal innate defense. © 2005 Steele et al.


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Details

Item Type: Article
Status: Published
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Steele, C
Rapaka, RR
Metz, A
Pop, SM
Williams, DL
Gordon, S
Kolls, JKjkk23@pitt.eduJKK23
Brown, GD
Contributors:
ContributionContributors NameEmailPitt UsernameORCID
EditorFiller, Scott G.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Centers: Other Centers, Institutes, or Units > Center for Clinical Pharmacology
Date: 1 December 2005
Date Type: Publication
Journal or Publication Title: PLoS Pathogens
Volume: 1
Number: 4
Page Range: 0323 - 0334
DOI or Unique Handle: 10.1371/journal.ppat.0010042
Refereed: Yes
ISSN: 1553-7366
PubMed ID: 16344862
Date Deposited: 11 Jul 2012 18:01
Last Modified: 02 Feb 2019 16:56
URI: http://d-scholarship.pitt.edu/id/eprint/12838

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