1. Listeria monocytogenes (delta-actA mutant) infection in tumor necrosis factor receptor p55-deficient neonatal mice.
- Author
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Sonje MB, Abram M, Stenzel W, and Deckert M
- Subjects
- Animals, Animals, Newborn, Brain pathology, Chemokine CCL2 biosynthesis, Chemokine CCL3 biosynthesis, Chemokine CCL5 biosynthesis, Disease Models, Animal, Female, Gene Expression Profiling, Indoleamine-Pyrrole 2,3,-Dioxygenase biosynthesis, Interferon-gamma biosynthesis, Interleukin-10 biosynthesis, Interleukin-12 Subunit p40 biosynthesis, Listeria monocytogenes pathogenicity, Listeriosis microbiology, Listeriosis pathology, Liver pathology, Male, Mice, Mice, Inbred C57BL, Mice, Knockout, Necrosis pathology, Nitric Oxide Synthase Type II biosynthesis, RNA, Messenger biosynthesis, Spleen pathology, Tumor Necrosis Factor-alpha biosynthesis, Bacterial Proteins genetics, Gene Deletion, Listeria monocytogenes genetics, Listeria monocytogenes immunology, Listeriosis immunology, Membrane Proteins genetics, Receptors, Tumor Necrosis Factor deficiency, Receptors, Tumor Necrosis Factor immunology
- Abstract
Using TNF receptor 1 knock out (TNFR1KO) mice, we investigated the role played by TNFR1 in immune regulation during neonatal listeriosis. Induction of protective immune response in wild type pups resulted in the prompt control of infection with an attenuated DeltaactA mutant Listeria monocytogenes, accompanied by enhanced hepatic expression of mRNA for IFN-gamma, TNF-alpha, and IL-10. Conversely, the lack of TNFR1 signalling in TNFR1KO neonatal mice resulted in substantial changes in the profile of inflammatory mediators and ultimately fatal outcome of the infected pups. Despite remarkable increase in indoleamine 2, 3-dioxygenase (IDO) and inducible nitric oxide synthase (iNOS) mRNA detected in the liver of TNFR1KO mice, bacterial proliferation was unrestrained. Increased mRNA expression of IDO, iNOS, TNF-alpha, IFN-gamma, MCP-1, and MIP-1alpha was found in the spleens of infected KO mice, and in the brains mRNA encoding iNOS, IDO, IFN-gamma, IL-12p40, IL-10, and RANTES was also upregulated. Large necrotic lesions consisting of granulocytes and macrophages were scattered throughout the liver of these mice. TNFR1KO neonates were unable to clear neutrophils and switch from the innate immune response to a specific reaction mediated by T cells. These results prove that TNF-alpha signalling is crucial and irreplaceable in antilisterial protection during the neonatal period., (Copyright 2010 Elsevier Ltd. All rights reserved.)
- Published
- 2010
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