Submitted September 27, 2005
Accepted June 24, 2006
The 
-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-
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-
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 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 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.
