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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.


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Submitted September 27, 2005
Accepted June 24, 2006

The {beta}-glucan receptor Dectin-1 functions together with TLR2 to mediated macrophage activation by mycobacteria

Mahesh Yadav and Jeffrey S Schorey*

Department of Biological Sciences, Center for Tropical Disease Research, University of Notre Dame

* Corresponding author; email: schorey.1{at}nd.edu.

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 MAPK activation and TNF-{alpha} production in macrophage infected with M. avium or M. smegmatis is dependent on MyD88 and TLR2 but not TLR4, MR or CR3. Interestingly, the TLR2 mediated production of TNF-{alpha} by macrophages infected with M. smegmatis required the {beta}-glucan receptor Dectin-1. A similar requirement for Dectin-1 in TNF-{alpha} production was observed for macrophages infected with M. bovis BCG, M. phlei, M. avium 2151-rough and M. tuberculosis H37Ra. The limited production of TNF-{alpha} by virulent M. avium 724 and M. tuberculosis H37Rv was not dependent on Dectin-1. Furthermore, Dectin-1 facilitated IL-6, RANTES and 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 pro-inflammatory response to a mycobacterial infection.


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