engleski

Patohistological changes in the liver and brain of neonatal TNFR1 knock out mice during Listeria monocytogenes infection

Listeria monocytogenes infection causes serious morbidity during the fetal and neonatal period. In order to determine the importance of TNF-α and TNFR1 signalling in antilisterial immunity, neonatal TNFR1 KO mice were infected with L. monocytogenes. The course of infection, pathological changes, cellular response and expression of different mediators in neonatal liver and brain were studied. Two days old TNFR1 KO mice and age-matched C57BL/6 controls were i.p. infected with actA deficient L. monocytogenes. Tissue sections were analysed using immunohistochemistry. RT-PCR was used to delineate the time course of the local, liver and brain, expression of mRNA encoding IFN-γ , TNF- , iNOS and IDO. 100% of the TNR1 KO mice succumbed while all C57BL/6 survived the infection. The impaired clearance of bacteria from the organs of TNFR1 KO mice resulted in development of necrotic hepatitis, meningoencephalitis and brain abscesses. In neonatal control mice the infection resulted in weak induction of hepatic and brain mRNA for TNF-α and IFN-γ . On contrary, in the liver of TNR1 KO mice these cytokines were not up-regulated, but IFN- γ was strongly enhanced in the brain tissue. De novo synthesis of iNOS and increased expression of mRNA for IDO were detected in the liver and brain of KO mice. C57BL/6 neonatal mice successfully face the L. monocytogenes infection. The course of listeriosis and mortality rate of TNFR1 KO mice shows the critical importance of TNFR1 in antilisterial immunity. Disturbance of the inflammatory mediators’ production implies the complex role of TNF-α in neonatal immune response against L. monocytogenes.

L. monocytogenes; TNFR1; neonatal mice

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