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

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dc.contributor.authorSteele, Chaden_ZA
dc.contributor.authorRapaka, Rekha Ren_ZA
dc.contributor.authorMetz, Allisonen_ZA
dc.contributor.authorPop, Shannon Men_ZA
dc.contributor.authorWilliams, David Len_ZA
dc.contributor.authorGordon, Siamonen_ZA
dc.contributor.authorKolls, Jay Ken_ZA
dc.contributor.authorBrown, Gordon Den_ZA
dc.date.accessioned2015-11-18T07:06:56Z
dc.date.available2015-11-18T07:06:56Z
dc.date.issued2005en_ZA
dc.description.abstractAlveolar 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.en_ZA
dc.identifier.apacitationSteele, C., Rapaka, R. R., Metz, A., Pop, S. M., Williams, D. L., Gordon, S., ... Brown, G. D. (2005). The beta-glucan receptor dectin-1 recognizes specific morphologies of Aspergillus fumigatus. <i>PLoS One</i>, http://hdl.handle.net/11427/15120en_ZA
dc.identifier.chicagocitationSteele, Chad, Rekha R Rapaka, Allison Metz, Shannon M Pop, David L Williams, Siamon Gordon, Jay K Kolls, and Gordon D Brown "The beta-glucan receptor dectin-1 recognizes specific morphologies of Aspergillus fumigatus." <i>PLoS One</i> (2005) http://hdl.handle.net/11427/15120en_ZA
dc.identifier.citationSteele, C., Rapaka, R. R., Metz, A., Pop, S. M., Williams, D. L., Gordon, S., ... & Brown, G. D. (2005). The beta-glucan receptor dectin-1 recognizes specific morphologies of Aspergillus fumigatus. PLoS Pathog, 1(4), e42. doi:10.1371/journal.ppat.0010042en_ZA
dc.identifier.ris TY - Journal Article AU - Steele, Chad AU - Rapaka, Rekha R AU - Metz, Allison AU - Pop, Shannon M AU - Williams, David L AU - Gordon, Siamon AU - Kolls, Jay K AU - Brown, Gordon D AB - 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. DA - 2005 DB - OpenUCT DO - 10.1371/journal.ppat.0010042 DP - University of Cape Town J1 - PLoS One LK - https://open.uct.ac.za PB - University of Cape Town PY - 2005 T1 - The beta-glucan receptor dectin-1 recognizes specific morphologies of Aspergillus fumigatus TI - The beta-glucan receptor dectin-1 recognizes specific morphologies of Aspergillus fumigatus UR - http://hdl.handle.net/11427/15120 ER - en_ZA
dc.identifier.urihttp://hdl.handle.net/11427/15120
dc.identifier.urihttp://dx.doi.org/10.1371/journal.ppat.0010042
dc.identifier.vancouvercitationSteele C, Rapaka RR, Metz A, Pop SM, Williams DL, Gordon S, et al. The beta-glucan receptor dectin-1 recognizes specific morphologies of Aspergillus fumigatus. PLoS One. 2005; http://hdl.handle.net/11427/15120.en_ZA
dc.language.isoengen_ZA
dc.publisherPublic Library of Scienceen_ZA
dc.publisher.departmentInstitute of Infectious Disease and Molecular Medicineen_ZA
dc.publisher.facultyFaculty of Health Sciencesen_ZA
dc.publisher.institutionUniversity of Cape Town
dc.rightsThis is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.en_ZA
dc.rights.holder© 2005 Steele et alen_ZA
dc.rights.urihttp://creativecommons.org/licenses/by/4.0en_ZA
dc.sourcePLoS Oneen_ZA
dc.source.urihttp://journals.plos.org/plospathogensen_ZA
dc.subject.otherAspergillus fumigatusen_ZA
dc.subject.otherAlveolar macrophagesen_ZA
dc.subject.otherCytokinesen_ZA
dc.subject.otherChemokinesen_ZA
dc.subject.otherInflammationen_ZA
dc.subject.otherMacrophagesen_ZA
dc.subject.otherToll-like receptorsen_ZA
dc.subject.otherGlucansen_ZA
dc.titleThe beta-glucan receptor dectin-1 recognizes specific morphologies of Aspergillus fumigatusen_ZA
dc.typeJournal Articleen_ZA
uct.type.filetypeText
uct.type.filetypeImage
uct.type.publicationResearchen_ZA
uct.type.resourceArticleen_ZA
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