Naslov
Tumor necrosis factor receptor 55 is required for a protective immune response to systemic Listeria monocytogenes infection in newborn mice

Autori
Bubonja, Marina ; Stenzel, Werner ; Deckert, Martina ; Abram, Maja

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, neobjavljeni rad, znanstveni

Skup
Annual Meeting of the Croatian Immunological Society

Mjesto i datum
Šibenik, Hrvatska, 09.10.2008. - 12.10.2008

Vrsta sudjelovanja
Predavanje

Vrsta recenzije
Nije recenziran

Ključne riječi
IDO; IFN-gamma; iNOS; Listeria monocytogenes; neonatal mice; TNFR1KO

Sažetak
Infection by Listeria monocytogenes causes serious morbidity and mortality durint the neonatal period. Using TNF receptor 1 knock out (TNFR1KO) mice, we investigated the role of 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 actA mutant L. monocytogenes, accompanied by enhanced hepatic expression of mRNA for IFN-gamma and TNF-alpha. The lack of TNFR1 signalling resulted in substantial changes in the inflammatory mediators profile and ultimately fatal outcome of infected pups, which experienced increasingly severe hepatitis, meningitis and brain abscesses. Despite remarkable increase in indoleamine dioxygenase (IDO) and inducible nitric oxide synthase (iNOS) mRNA in the liver of TNFR1KO mice, unrestrained bacterial proliferation was observed. Increased mRNA expression of IDO and iNOS as well as TNF-alpha and IFN-gamma was found in the spleen of infected KO mice whereas in their brain tissue mRNA encoding iNOS, IDO and IFN-gamma was upregulated. In addition to observed exaggerated production of inflammatory mediators, large necrotic lesions consisting of granulocytes and macrophages were found throughout the liver tissue of these mice. TNFR1KO neonates seem to be unable to clear and replace shorter-lived neutrophils in inflammatory lesions with T-cells. Loss of granuloma integrity led to a progressive L. monocytogens infection. The results prove that TNF-alpha signalling through TNFR1 mediating mRNA expression of different inflammatory mediators is crucial and irreplaceable in antilisterial protection during neonatal period.

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti

POVEZANOST RADA