dc.creator | Serezani, C. Henrique | |
dc.creator | Kane, Steve | |
dc.creator | Collins, Latima | |
dc.creator | Marques, Mariana Morato | |
dc.creator | Osterholzer, John J. | |
dc.creator | Peters-Golden, Marc | |
dc.date.accessioned | 2013-11-07T11:26:00Z | |
dc.date.accessioned | 2018-07-04T16:16:43Z | |
dc.date.available | 2013-11-07T11:26:00Z | |
dc.date.available | 2018-07-04T16:16:43Z | |
dc.date.created | 2013-11-07T11:26:00Z | |
dc.date.issued | 2012 | |
dc.identifier | JOURNAL OF IMMUNOLOGY, BETHESDA, v. 189, n. 2, p. 906-915, JUL 15, 2012 | |
dc.identifier | 0022-1767 | |
dc.identifier | http://www.producao.usp.br/handle/BDPI/43019 | |
dc.identifier | 10.4049/jimmunol.1200257 | |
dc.identifier | http://dx.doi.org/10.4049/jimmunol.1200257 | |
dc.identifier.uri | http://repositorioslatinoamericanos.uchile.cl/handle/2250/1633776 | |
dc.description.abstract | Pattern recognition receptors for fungi include dectin-1 and mannose receptor, and these mediate phagocytosis, as well as production of cytokines, reactive oxygen species, and the lipid mediator leukotriene B-4 (LTB4). The influence of G protein-coupled receptor ligands such as LTB4 on fungal pattern recognition receptor expression is unknown. In this study, we investigated the role of LTB4 signaling in dectin-1 expression and responsiveness in macrophages. Genetic and pharmacologic approaches showed that LTB4 production and signaling through its high-affinity G protein-coupled receptor leukotriene B4 receptor 1 (BLT1) direct dectin-1-dependent binding, ingestion, and cytokine production both in vitro and in vivo. Impaired responses to fungal glucans correlated with lower dectin-1 expression in macrophages from leukotriene (LT)- and BLT1-deficent mice than their wildtype counterparts. LTB4 increased the expression of the transcription factor responsible for dectin-1 expression, PU.1, and PU.1 small interfering RNA abolished LTB4-enhanced dectin-1 expression. GM-CSF controls PU.1 expression, and this cytokine was decreased in LT-deficient macrophages. Addition of GM-CSF to LT-deficient cells restored expression of dectin-1 and PU.1, as well as dectin-1 responsiveness. In addition, LTB4 effects on dectin-1, PU.1, and cytokine production were blunted in GM-CSF-/- macrophages. Our results identify LTB4-BLT1 signaling as an unrecognized controller of dectin-1 transcription via GM-CSF and PU.1 that is required for fungi-protective host responses. The Journal of Immunology, 2012, 189: 906-915. | |
dc.language | eng | |
dc.publisher | AMER ASSOC IMMUNOLOGISTS | |
dc.publisher | BETHESDA | |
dc.relation | JOURNAL OF IMMUNOLOGY | |
dc.rights | Copyright AMER ASSOC IMMUNOLOGISTS | |
dc.rights | restrictedAccess | |
dc.title | Macrophage Dectin-1 Expression Is Controlled by Leukotriene B-4 via a GM-CSF/PU.1 Axis | |
dc.type | Artículos de revistas | |