Listeria monocytogenes (delta-actA mutant) infection in tumor necrosis factor receptor p55-deficient neonatal mice.
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.
Sonje
Marina Bubonja
MB
Department of Microbiology, Faculty of Medicine, University of Rijeka, Rijeka, Croatia. mbubonja@medri.hr
Abram
Maja
M
Stenzel
Werner
W
Deckert
Martina
M
D000818:Animals; D000831:Animals, Newborn; D001426:Bacterial Proteins / Q000235:genetics*; D001921:Brain / Q000473:pathology; D018932:Chemokine CCL2 / Q000096:biosynthesis; D054405:Chemokine CCL3 / Q000096:biosynthesis; D018946:Chemokine CCL5 / Q000096:biosynthesis; D004195:Disease Models, Animal; D005260:Female; D017353:Gene Deletion; D020869:Gene Expression Profiling; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000096:biosynthesis; D007371:Interferon-gamma / Q000096:biosynthesis; D016753:Interleukin-10 / Q000096:biosynthesis; D053762:Interleukin-12 Subunit p40 / Q000096:biosynthesis; D008089:Listeria monocytogenes / Q000235:genetics* / Q000276:immunology* / Q000472:pathogenicity; D008088:Listeriosis / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D008099:Liver / Q000473:pathology; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009336:Necrosis / Q000473:pathology; D052247:Nitric Oxide Synthase Type II / Q000096:biosynthesis; D012333:RNA, Messenger / Q000096:biosynthesis; D018124:Receptors, Tumor Necrosis Factor / Q000172:deficiency* / Q000276:immunology*; D013154:Spleen / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D001426:Bacterial Proteins; C491768:Ccl2 protein, mouse; C503460:Ccl5 protein, mouse; D018932:Chemokine CCL2; D054405:Chemokine CCL3; D018946:Chemokine CCL5; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D053762:Interleukin-12 Subunit p40; D008565:Membrane Proteins; D012333:RNA, Messenger; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; C072980:actA protein, Listeria monocytogenes; D007371:Interferon-gamma; D052247:Nitric Oxide Synthase Type II