| First Author | Tsuji NM | Year | 2004 |
| Journal | Int Immunol | Volume | 16 |
| Issue | 2 | Pages | 335-43 |
| PubMed ID | 14734619 | Mgi Jnum | J:88971 |
| Mgi Id | MGI:3037522 | Doi | 10.1093/intimm/dxh041 |
| Citation | Tsuji NM, et al. (2004) Roles of caspase-1 in Listeria infection in mice. Int Immunol 16(2):335-43 |
| abstractText | Caspase-1 [IL-1beta-converting enzyme (ICE)] processes substrate precursor molecules to yield the biologically active form of IL-1beta and IL-18, both of which are considered to play important roles in the host defense by activation of both innate and adaptive immunity. We evaluated the immune response of caspase-1(-/-) mice to Listeria monocytogenes (LM) infection. LM eradication in the early phase of infection was impaired in the mutant mice with a prominent decrease in IL-18 and IFN-gamma production, but not in IL-12. Caspase-1(-/-) spleen cells including dendritic cells and NK cells produced less IFN-gamma in response to heat-killed LM than wild-type cells in vitro. IFN-gamma production and bactericidal activity in LM-infected caspase-1(-/-) mice was reconstituted to normal levels by adding back IL-18 at the initial phase of infection, suggesting that the lack of this cytokine is primarily responsible for the susceptibility of caspase-1(-/-) mice against LM infection. Moreover, IFN-gamma injection of caspase-1(-/-) mice corrected the deficiency in pathogen clearance. In contrast, LM-specific acquired immunity in caspase-1(-/-) mice was normal and they successfully cleared the pathogen following secondary infection, in spite of a moderate skewing of cytokine profile to T(h)2 when compared to wild-type mice. These data shed light on the importance of caspase-1-mediated IL-18 processing in innate immunity against facultative intracellular pathogens. |
