NDLI: Macrophage dectin-1 expression is controlled by leukotriene B4 via a GM-CSF/PU.1 axis.

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Macrophage dectin-1 expression is controlled by leukotriene B4 via a GM-CSF/PU.1 axis.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Osterholzer, John J. Serezani, C. Henrique Kane, Steve Morato-Marques, Mariana Collins, Latima Peters-Golden, Marc
Description	Country affiliation: United States Author Affiliation: Serezani CH ( Department of Internal Medicine, University of Michigan Health System, Ann Arbor, MI 48109, USA.)
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) (LTB(4)). The influence of G protein-coupled receptor ligands such as LTB(4) on fungal pattern recognition receptor expression is unknown. In this study, we investigated the role of LTB(4) signaling in dectin-1 expression and responsiveness in macrophages. Genetic and pharmacologic approaches showed that LTB(4) production and signaling through its high-affinity G protein-coupled receptor leukotriene B(4) 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 wild-type counterparts. LTB(4) increased the expression of the transcription factor responsible for dectin-1 expression, PU.1, and PU.1 small interfering RNA abolished LTB(4)-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, LTB(4) effects on dectin-1, PU.1, and cytokine production were blunted in GM-CSF(-/-) macrophages. Our results identify LTB(4)-BLT1 signaling as an unrecognized controller of dectin-1 transcription via GM-CSF and PU.1 that is required for fungi-protective host responses.
ISSN	00221767
e-ISSN	15506606
DOI	10.4049/jimmunol.1200257
Journal	The Journal of Immunology
Issue Number	2
Volume Number	189
Language	English
Publisher	The American Association of Immunologists
Publisher Date	2012-07-15
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Granulocyte-macrophage Colony-stimulating Factor Physiology Lectins, C-type Biosynthesis Leukotriene B4 Macrophages, Alveolar Immunology Macrophages, Peritoneal Proto-oncogene Proteins Trans-activators Animals Candida Albicans Cells, Cultured Deficiency Genetics Metabolism Microbiology Mice Mice, 129 Strain Mice, Inbred C57bl Mice, Knockout Receptors, Leukotriene B4 Transcription, Genetic Research Support, N.i.h., Extramural Research Support, Non-u.s. Gov't Discipline Immunology
Content Type	Text
Resource Type	Article
Subject	Immunology and Allergy Immunology

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Macrophage dectin-1 expression is controlled by leukotriene B4 via a GM-CSF/PU.1 axis.

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Macrophage dectin-1 expression is controlled by leukotriene B4 via a GM-CSF/PU.1 axis

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