| First Author | Garlanda C | Year | 2007 |
| Journal | J Immunol | Volume | 179 |
| Issue | 5 | Pages | 3119-25 |
| PubMed ID | 17709526 | Mgi Jnum | J:151829 |
| Mgi Id | MGI:4355316 | Doi | 10.4049/jimmunol.179.5.3119 |
| Citation | Garlanda C, et al. (2007) Damping excessive inflammation and tissue damage in Mycobacterium tuberculosis infection by Toll IL-1 receptor 8/single Ig IL-1-related receptor, a negative regulator of IL-1/TLR signaling. J Immunol 179(5):3119-25 |
| abstractText | Toll IL-1R 8/single Ig IL-1-related receptor (TIR8/SIGIRR) is a member of the IL-1R family, expressed by epithelial tissues and immature dendritic cells, and is regarded as a negative regulator of TLR/IL-1R signaling. Tir8-deficient mice were rapidly killed by intranasal administration of low doses of Mycobacterium tuberculosis, despite controlling efficiently the number of viable bacilli in different organs. Tir8(-/-)-infected mice showed an increased number of neutrophils and macrophages in the lungs; however, mycobacteria-specific CD4 and CD8 T cells were similar in Tir8(-/-) and Tir8(+/+) mice. Exaggerated mortality of Tir8(-/-) mice was due to massive liver necrosis and was accompanied by increased levels of IL-1beta and TNF-alpha in lung mononuclear cells and serum, as well as by increased production of IL-1beta and TNF-alpha by M. tuberculosis-infected dendritic cells in vitro. Accordingly, blocking IL-1beta and TNF-alpha with a mix of anti-cytokine Abs, significantly prolonged survival of Tir8(-/-) mice. Thus, TIR8/SIGIRR plays a key role in damping inflammation and tissue damage in M. tuberculosis infection. |
