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Infection and Immunity, July 2006, p. 3783-3789, Vol. 74, No. 7
0019-9567/06/$08.00+0     doi:10.1128/IAI.00022-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Cell Wall-Mediated Neuronal Damage in Early Sepsis

Carlos J. Orihuela ,1,{dagger},{ddagger} Sophie Fillon,1,{dagger} S. Hope Smith-Sielicki,1 Karim C. El Kasmi,1 Geli Gao,1 Konstantinos Soulis,1,§ Avinash Patil,2 Peter J. Murray,1 and Elaine I. Tuomanen1*

Department of Infectious Diseases, St. Jude Children's Research Hospital, 332 N. Lauderdale Rd., Memphis, Tennessee 38105,1 University of Tennessee Medical School, Dunlap Ave., Memphis, Tennessee 381632

Received 4 January 2006/ Returned for modification 27 March 2006/ Accepted 20 April 2006

Neuronal dysfunction can occur in the course of sepsis without meningitis. Sepsis-associated neuronal damage (SAND) was observed in the hippocampus within hours in experimental pneumococcal bacteremia. Intravascular challenge with purified bacterial cell wall recapitulated SAND. SAND persisted in PAFr–/– mice but was partially mitigated in mice lacking cell wall recognition proteins TLR2 and Nod2 and in mice overexpressing interleukin-10 (IL-10) in macrophages. Thus, cell wall drives SAND through IL-10-repressible inflammatory events. Treatment with CDP-choline ameliorated SAND, suggesting that it may be an effective adjunctive therapy to increase survival and reduce organ damage in sepsis.

* Corresponding author. Mailing address: Infectious Diseases, St. Jude Children's Research Hospital, Mailstop 320 IRC 8057, 332 N. Lauderdale Rd., Memphis, TN 38105. Phone: (901) 495-3114. Fax: (901) 495-3099. E-mail: elaine.tuomanen{at}stjude.org.

Editor: J. N. Weiser

{dagger} These authors contributed equally to this work.

{ddagger} Present address: Department of Microbiology and Immunology, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, MC7758, San Antonio, TX 78229-3900.

§ Present address: Papaflessa 152, 185 46 Peiraias, Greece.

Infection and Immunity, July 2006, p. 3783-3789, Vol. 74, No. 7
0019-9567/06/$08.00+0     doi:10.1128/IAI.00022-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.





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