| Autor: |
Mittal R; Division of Infectious Diseases, Department of Pathology, Childrens Hospital Los Angeles and University of Southern California Keck School of Medicine, Los Angeles, CA 90027, USA., Gonzalez-Gomez I, Panigrahy A, Goth K, Bonnet R, Prasadarao NV |
| Jazyk: |
angličtina |
| Zdroj: |
The Journal of experimental medicine [J Exp Med] 2010 Jun 07; Vol. 207 (6), pp. 1307-19. Date of Electronic Publication: 2010 May 24. |
| DOI: |
10.1084/jem.20092265 |
| Abstrakt: |
Ineffectiveness of antibiotics in treating neonatal Escherichia coli K1 meningitis and the emergence of antibiotic-resistant strains evidently warrants new prevention strategies. We observed that administration of interleukin (IL)-10 during high-grade bacteremia clears antibiotic-sensitive and -resistant E. coli from blood of infected mice. Micro-CT studies of brains from infected animals displayed gross morphological changes similar to those observed in infected human neonates. In mice, IL-10, but not antibiotic or anti-TNF antibody treatment prevented brain damage caused by E. coli. IL-10 administration elevated CR3 expression in neutrophils and macrophages of infected mice, whereas infected and untreated mice displayed increased expression of FcgammaRI and TLR2. Neutrophils or macrophages pretreated with IL-10 ex vivo exhibited a significantly greater microbicidal activity against E. coli compared with cells isolated from wild-type or IL-10-/- mice. The protective effect of IL-10 was abrogated when CR3 was knocked-down in vivo by siRNA. The increased expression of CR3 in phagocytes was caused by inhibition of prostaglandin E-2 (PGE-2) levels, which were significantly increased in neutrophils and macrophages upon E. coli infection. These findings describe a novel modality of IL-10-mediated E. coli clearance by diverting the entry of bacteria via CR3 and preventing PGE-2 formation in neonatal meningitis. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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