| First Author | Jayaraman P | Year | 2013 |
| Journal | J Immunol | Volume | 190 |
| Issue | 8 | Pages | 4196-204 |
| PubMed ID | 23487424 | Mgi Jnum | J:195120 |
| Mgi Id | MGI:5476558 | Doi | 10.4049/jimmunol.1202688 |
| Citation | Jayaraman P, et al. (2013) IL-1beta Promotes Antimicrobial Immunity in Macrophages by Regulating TNFR Signaling and Caspase-3 Activation. J Immunol 190(8):4196-204 |
| abstractText | In vivo control of Mycobacterium tuberculosis reflects the balance between host immunity and bacterial evasion strategies. Effector Th1 cells that mediate protective immunity by depriving the bacterium of its intracellular niche are regulated to prevent overexuberant inflammation. One key immunoregulatory molecule is Tim3. Although Tim3 is generally recognized to downregulate Th1 responses, we recently described that its interaction with Galectin-9 expressed by M. tuberculosis-infected macrophages stimulates IL-1beta secretion, which is essential for survival in the mouse model. Why IL-1beta is required for host resistance to M. tuberculosis infection is unknown. In this article, we show that IL-1beta directly kills M. tuberculosis in murine and human macrophages and does so through the recruitment of other antimicrobial effector molecules. IL-1beta directly augments TNF signaling in macrophages through the upregulation of TNF secretion and TNFR1 cell surface expression, and results in activation of caspase-3. Thus, IL-1beta and downstream TNF production lead to caspase-dependent restriction of intracellular M. tuberculosis growth. |
