Roles of caspase-1 in Listeria infection in mice.

Abstract

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.

• Authors: Noriko M Tsuji, Hiroko Tsutsui, Ekihiro Seki, Keisuke Kuida, Haruki Okamura, Kenji Nakanishi, Richard A Flavell
• Journal: International immunology (Int Immunol) Vol. 16 Issue 2 Pg. 335-43 (Feb 2004) ISSN: 0953-8178 [Print] England
• PMID: 14734619 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Interleukin-1
• Interleukin-18
• Interleukin-6
• Tumor Necrosis Factor-alpha
• Interleukin-12
• Interferon-gamma
• Caspase 1

Topics

• Animals
• Caspase 1 (genetics, immunology)
• Dendritic Cells (immunology, metabolism)
• Interferon-gamma (biosynthesis)
• Interleukin-1 (immunology, metabolism)
• Interleukin-12 (biosynthesis)
• Interleukin-18 (immunology, metabolism)
• Interleukin-6 (biosynthesis)
• Killer Cells, Natural (immunology, metabolism)
• Listeriosis (enzymology, immunology)
• Lymphocyte Activation (genetics, immunology)
• Mice
• Mice, Knockout
• Th2 Cells (immunology, metabolism)
• Tumor Necrosis Factor-alpha (biosynthesis)