| First Author | Yadav M | Year | 2006 |
| Journal | Blood | Volume | 108 |
| Issue | 9 | Pages | 3168-75 |
| PubMed ID | 16825490 | Mgi Jnum | J:140459 |
| Mgi Id | MGI:3813803 | Doi | 10.1182/blood-2006-05-024406 |
| Citation | Yadav M, et al. (2006) The beta-glucan receptor dectin-1 functions together with TLR2 to mediate macrophage activation by mycobacteria. Blood 108(9):3168-75 |
| abstractText | 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-alpha (TNF-alpha) 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-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 Bacillus Calmette-Guerin (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 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. |
