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Infection and Immunity, February 1999, p. 595-601, Vol. 67, No. 2
Departments of
Pediatrics,1
Medicine,3 and
Pathology,4 University of Rochester
School of Medicine and Dentistry, Rochester, New York 14642, and
Department of Microbiology, University of Alabama at
Birmingham, Birmingham, Alabama 352942
Received 23 July 1998/Returned for modification 3 September
1998/Accepted 4 November 1998
Tumor necrosis factor alpha (TNF-
0019-9567/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.
Tumor Necrosis Factor Alpha Receptor I Is Important
for Survival from Streptococcus pneumoniae
Infections
) is important in resistance to
various microorganisms and provides signals to the target cells
through two different receptors, TNF-
receptor I (TNFRI) (p55
receptor) and TNFRII (p75 receptor). To delineate the
significance of the two different signaling pathways in resisting
infections with extracellular bacteria, we examined the resistance of
mice to Streptococcus pneumoniae (serotype 6B). TNF-
needs to be present early in infections, since one injection of
wild-type mice with anti-TNF-
leads to an increased
susceptibility of these mice to S. pneumoniae. TNF-
signaling through the p55 receptor (but not the p75 receptor) is
crucial in resisting S. pneumoniae infections, because
intraperitoneal injection of 100 CFU/mouse killed p55-deficient mice by
day 2 of infection, whereas 1,000,000 CFU/mouse was needed to kill half
of the control mice. p55-deficient mice do not show evidence of a
deficient acute-phase response. All three types of mice (p55 deficient,
p75 deficient, and normal) showed comparable rises in the levels of two
acute-phase proteins (serum amyloid P and C3) at 24, 48, and 72 h
after the experimental infections, and all of the mice showed
comparable influxes of neutrophils to the site of infection. Finally,
it was demonstrated that p55-deficient mice can be protected
from the lethal effects of S. pneumoniae infection by
injection of antibodies specific for S. pneumoniae polysaccharide capsule.
*
Corresponding author. Mailing address: University of
Rochester School of Medicine, 601 Elmwood Ave., Box 777, Rochester, NY 14642. Phone: (716) 275-7963. Fax: (716) 271-7512. E-mail:
moon{at}vaccine.rochester.edu.
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