The membrane form of tumor necrosis factor is sufficient to mediate partial innate immunity to Francisella tularensis live vaccine strain.
Here we characterize Francisella tularensis live vaccine strain (LVS) infection in total tumor necrosis factor (TNF) knockout (KO) mice and in transgenic mice expressing only the membrane form of TNF (memTNF). MemTNF mice, but not TNF KO mice, survived low-dose, sublethal LVS infections. Splenic nitric oxide production was impaired in infected memTNF mice and was absent in infected TNF KO mice. Spleen cell production of interferon-gamma, RANTES, and monocyte chemotactic protein-1 was elevated in TNF KO mice, compared with that in WT mice, by days 4-5 after infection, along with transiently increased numbers of CCR2(+) cells, whereas memTNF mice had an intermediate phenotype. By day 6 after infection, TNF KO mice, but not memTNF mice, exhibited massive apoptosis in spleens and livers, which shortly preceded their death. Thus, memTNF partially functions to regulate chemokine expression, cell recruitment, and nitric oxide production during primary LVS infection and protects against the induction of apoptosis observed in TNF KO mice.
Cowley
Siobhán C
SC
Laboratory of Mycobacterial Diseases and Cellular Immunology, Center for Biologics Research and Evaluation, US Food and Drug Administration, Rockville, MD 20852, USA. siobhan.cowley@fda.hhs.gov
Goldberg
Michael F
MF
Ho
J Anthony
JA
Elkins
Karen L
KL
D000818:Animals; D017209:Apoptosis; D001219:Aspartate Aminotransferases / Q000097:blood; D001428:Bacterial Vaccines / Q000276:immunology*; D002455:Cell Division; D002462:Cell Membrane / Q000276:immunology*; D005604:Francisella tularensis / Q000254:growth & development / Q000276:immunology*; D007113:Immunity, Innate; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors; D017382:Reactive Oxygen Species; D013047:Specific Pathogen-Free Organisms; D013154:Spleen / Q000276:immunology; D014406:Tularemia / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000172:deficiency / Q000235:genetics / Q000276:immunology*; D014613:Vaccines, Attenuated / Q000276:immunology*
D001428:Bacterial Vaccines; D017382:Reactive Oxygen Species; D014409:Tumor Necrosis Factor-alpha; D014613:Vaccines, Attenuated; D052247:Nitric Oxide Synthase Type II; D001219:Aspartate Aminotransferases