Effect of deficiency of tumor necrosis factor alpha or both of its receptors on Streptococcus pneumoniae central nervous system infection and peritonitis.
Tumor necrosis factor alpha (TNF-alpha) and TNF-beta are key mediators in bacterial inflammation. We therefore examined the role of TNF-alpha and its two receptors in murine pneumococcal central nervous system infection. TNF-alpha knockout mice and age- and sex-matched controls and TNF receptor (p55 and p75)-deficient mice and heterozygous littermates were infected intracerebrally with a Streptococcus pneumoniae type 3 strain. Mice were monitored until death or were killed 36 h after infection. Bacterial titers in blood, spleen, and brain homogenates were determined. Leukocyte infiltration and neuronal damage were assessed by histological scores. TNF-alpha-deficient mice died earlier than the controls after intracerebral infection although overall survival was similar. TNF-alpha deficiency did not inhibit leukocyte recruitment into the subarachnoid space and did not lead to an increased density of bacteria in brain homogenates. However, it caused a substantial rise of the concentration of S. pneumoniae cells in blood and spleen. Spleen bacterial titers were also increased in p55- and p75-deficient mice. TNF receptor-deficient mice showed decreased meningeal inflammation. Neuronal damage was not affected by either TNF-alpha or TNF receptor deficiency. In a murine model of pneumococcal peritonitis, 10(2) CFU of S. pneumoniae produced fatal peritonitis in TNF-alpha-deficient, but not wild-type, mice. Early leukocyte influx into the peritoneum was impaired in TNF-alpha-deficient mice. The lack of TNF-alpha or its receptors renders mice more susceptible to S. pneumoniae infections.
Wellmer
A
A
Departments of Neurology, University of Göttingen, Göttingen, Germany.
Gerber
J
J
Ragheb
J
J
Zysk
G
G
Kunst
T
T
Smirnov
A
A
Brück
W
W
Nau
R
R
D000328:Adult; D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000276:immunology*; D001927:Brain Diseases / Q000276:immunology*; D020806:Central Nervous System Bacterial Infections / Q000276:immunology*; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010538:Peritonitis / Q000276:immunology; D011008:Pneumococcal Infections / Q000276:immunology*; D018124:Receptors, Tumor Necrosis Factor / Q000235:genetics / Q000276:immunology*; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; D013296:Streptococcus pneumoniae / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000276:immunology*
D015703:Antigens, CD; D018124:Receptors, Tumor Necrosis Factor; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; D014409:Tumor Necrosis Factor-alpha