The β-glucan receptor dectin-1 functions together with TLR2 to mediate macrophage activation by mycobacteria
Open Access
- 1 November 2006
- journal article
- Published by American Society of Hematology in Blood
- Vol. 108 (9), 3168-3175
- https://doi.org/10.1182/blood-2006-05-024406
Abstract
Pattern recognition receptors (PRRs) play an essential role in a macrophage's response to mycobacterial infections. However, how these receptors work in concert to promote this macrophage response remains unclear. In this study, we used bone marrow–derived macrophages isolated from mannose receptor (MR), complement receptor 3 (CR3), MyD88, Toll-like receptor 4 (TLR4), and TLR2 knockout mice to examine the significance of these receptors in mediating a macrophage's response to a mycobacterial infection. We determined that mitogen-activated protein kinase (MAPK) activation and tumor necrosis factor-α (TNF-α) production in macrophage infected with Mycobacterium avium or M smegmatis is dependent on myeloid differentiation factor 88 (MyD88) and TLR2 but not TLR4, MR, or CR3. Interestingly, the TLR2-mediated production of TNF-α by macrophages infected with M smegmatis required the β-glucan receptor dectin-1. A similar requirement for dectin-1 in TNF-α production was observed for macrophages infected with M bovis Bacillus Calmette-Guerin (BCG), M phlei, M avium 2151-rough, and M tuberculosis H37Ra. The limited production of TNF-α by virulent M avium 724 and M tuberculosis H37Rv was not dependent on dectin-1. Furthermore, dectin-1 facilitated interleukin-6 (IL-6), RANTES (regulated on activation, normal T expressed and secreted), and granulocyte colony-stimulating factor (G-CSF) production by mycobacteria-infected macrophages. These are the first results to establish a significant role for dectin-1, in cooperation with TLR2, to activate a macrophage's proinflammatory response to a mycobacterial infection.This publication has 56 references indexed in Scilit:
- Glycopeptidolipids from Mycobacterium avium promote macrophage activation in a TLR2- and MyD88-dependent mannerJournal of Leukocyte Biology, 2006
- Elevated mitogen-activated protein kinase signalling and increased macrophage activation in cells infected with a glycopeptidolipid-deficient Mycobacterium aviumCellular Microbiology, 2006
- Mycobacterium Tuberculosis Heat Shock Proteins Use Diverse Toll-like Receptor Pathways to Activate Pro-inflammatory SignalsJournal of Biological Chemistry, 2005
- Differential Activation of the Transcription Factor Cyclic AMP Response Element Binding Protein (CREB) in Macrophages following Infection with Pathogenic and Nonpathogenic Mycobacteria and Role for CREB in Tumor Necrosis Factor Alpha ProductionInfection and Immunity, 2005
- Toll-like Receptor 2 and Mitogen- and Stress-activated Kinase 1 Are Effectors of Mycobacterium avium-induced Cyclooxygenase-2 Expression in MacrophagesOnline Journal of Public Health Informatics, 2004
- Revisiting the Structure of the Anti-neoplastic Glucans of Mycobacterium bovis Bacille Calmette-GuérinJournal of Biological Chemistry, 2004
- High Density Lipoprotein-induced Signaling of the MAPK Pathway Involves Scavenger Receptor Type BI-mediated Activation of RasOnline Journal of Public Health Informatics, 2003
- Dectin-1 Is A Major β-Glucan Receptor On MacrophagesThe Journal of Experimental Medicine, 2002
- The Importance of a β‐Glucan Receptor in the Nonopsonic Entry of NontypeableHaemophilus influenzaeinto Human Monocytic and Epithelial CellsThe Journal of Infectious Diseases, 2001
- Uptake of Pneumocystis carinii mediated by the macrophage mannose receptorNature, 1991