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Blood, 1 November 2006, Vol. 108, No. 9, pp. 3168-3175. Prepublished online as a Blood First Edition Paper on July 6, 2006; DOI 10.1182/blood-2006-05-024406. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2006-05-024406v1 108/9/3168    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Yadav, M. Articles by Schorey, J. S. Search for Related Content PubMed PubMed Citation Articles by Yadav, M. Articles by Schorey, J. S. Related Collections Signal Transduction Phagocytes Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  PHAGOCYTES The -glucan receptor dectin-1 functions together with TLR2 to mediate macrophage activation by mycobacteria Mahesh Yadav, and Jeffrey S. Schorey From the Department of Biological Sciences, Center for Tropical Disease Research and Training, University of Notre Dame, IN 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- (TNF-) 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- by macrophages infected with M smegmatis required the -glucan receptor dectin-1. A similar requirement for dectin-1 in TNF- 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- 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. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: A. Schwegmann and F. Brombacher Host-Directed Drug Targeting of Factors Hijacked by Pathogens Sci. Signal., July 22, 2008; 1(29): re8 - re8. [Abstract] [Full Text] [PDF] N. R. Patel, J. Zhu, S. D. Tachado, J. Zhang, Z. Wan, J. Saukkonen, and H. Koziel HIV Impairs TNF-{alpha} Mediated Macrophage Apoptotic Response to Mycobacterium tuberculosis J. Immunol., November 15, 2007; 179(10): 6973 - 6980. [Abstract] [Full Text] [PDF] A. G. Rothfuchs, A. Bafica, C. G. Feng, J. G. Egen, D. L. Williams, G. D. Brown, and A. Sher Dectin-1 Interaction with Mycobacterium tuberculosis Leads to Enhanced IL-12p40 Production by Splenic Dendritic Cells J. Immunol., September 15, 2007; 179(6): 3463 - 3471. [Abstract] [Full Text] [PDF] S. Chang, A. Dolganiuc, and G. Szabo Toll-like receptors 1 and 6 are involved in TLR2-mediated macrophage activation by hepatitis C virus core and NS3 proteins J. Leukoc. Biol., September 1, 2007; 82(3): 479 - 487. [Abstract] [Full Text] [PDF] K. M. Empey, M. Hollifield, and B. A. Garvy Exogenous Heat-Killed Escherichia coli Improves Alveolar Macrophage Activity and Reduces Pneumocystis carinii Lung Burden in Infant Mice Infect. Immun., July 1, 2007; 75(7): 3382 - 3393. [Abstract] [Full Text] [PDF] A. B. Schromm, J. Howe, A. J. Ulmer, K.-H. Wiesmuller, T. Seyberth, G. Jung, M. Rossle, M. H. J. Koch, T. Gutsmann, and K. Brandenburg Physicochemical and Biological Analysis of Synthetic Bacterial Lipopeptides: VALIDITY OF THE CONCEPT OF ENDOTOXIC CONFORMATION J. Biol. Chem., April 13, 2007; 282(15): 11030 - 11037. [Abstract] [Full Text] [PDF] H. S. Goodridge, R. M. Simmons, and D. M. Underhill Dectin-1 Stimulation by Candida albicans Yeast or Zymosan Triggers NFAT Activation in Macrophages and Dendritic Cells J. Immunol., March 1, 2007; 178(5): 3107 - 3115. [Abstract] [Full Text] [PDF]

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