| First Author | Kang TJ | Year | 2008 |
| Journal | Eur J Immunol | Volume | 38 |
| Issue | 6 | Pages | 1574-84 |
| PubMed ID | 18493980 | Mgi Jnum | J:136368 |
| Mgi Id | MGI:3796037 | Doi | 10.1002/eji.200838141 |
| Citation | Kang TJ, et al. (2008) Bacillus anthracis spores and lethal toxin induce IL-1beta via functionally distinct signaling pathways. Eur J Immunol 38(6):1574-84 |
| abstractText | Previous reports suggested that lethal toxin (LT)-induced caspase-1 activity and/or IL-1beta accounted for Bacillus anthracis (BA) infection lethality. In contrast, we now report that caspase-1-mediated IL-1beta expression in response to BA spores is required for anti-BA host defenses. Caspase-1(-/-) and IL-1beta(-/-) mice are more susceptible than wild-type (WT) mice to lethal BA infection, are less able to kill BA both in vivo and in vitro, and addition of rIL-1beta to macrophages from these mice restored killing in vitro. Non-germinating BA spores induced caspase-1 activity, IL-1beta and nitric oxide, by which BA are killed in WT but not in caspase-1(-/-) mice, suggesting that the spore itself stimulated inflammatory responses. While spores induced IL-1beta in LT-susceptible and -resistant macrophages, LT induced IL-1beta only in LT-susceptible macrophages. Cooperation between MyD88-dependent and -independent signaling pathways was required for spore-induced, but not LT-induced, IL-1beta. While both spores and LT induced caspase-1 activity and IL-1beta, LT did not induce IL-1beta mRNA, and spores did not induce cell death. Thus different components of the same bacterium each induce IL-1beta by distinct signaling pathways. Whereas the spore-induced IL-1beta limits BA infection, LT-induced IL-1beta enables BA to escape host defenses.Supporting Information for this article is available at www.wiley-vch.de/contents/jc_2040/2008/38141_s.pdf. |
