engleski

Impaired control of Listeria monocytogenes infection in neonatal mice lacking tumor necrosis factor receptor 1

Infection by Listeria monocytogenes causes serious morbidity and mortality during the neonatal period. Using TNF receptor 1 knock out (TNFR1KO) mice, we explored the role played by TNFR1 in immune regulation during neonatal listeriosis. Induction of protective immune response in wild type newborns resulted in the prompt control of infection with attenuated strain ∆actA-L. monocytogenes, accompanied by enhanced hepatic expression of mRNA for TNF-, IFN-, and IL-10. In contrast, TNFR1KO neonatal mice succumbed to infection due to an insufficient control of listeriosis. In spite of 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-, IFN-, MCP-1, and MIP-1 was found in the spleen of infected KO mice whereas in their brains mRNA encoding iNOS, IDO, IFN-γ, IL-12p40, IL-10, and RANTES were also upregulated. In addition to the exaggerated production of inflammatory mediators, large necrotic lesions consisting of macrophages and granulocytes were scattered throughout the liver of TNFR1KO mice. Mice lacking TNFR1 were unable to clear neutrophils and switch from the innate immune response to a specific reaction mediated by T-cells. Collectively, these findings illustrate a crucial role of TNFR1 signalling in antilisterial protection during the neonatal period.

Listeria monocytogens; neonatal; mice; tumor necrosis factor receptor

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