Cell wall-mediated neuronal damage in early sepsis.
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.
Orihuela
Carlos J
CJ
Infectious Diseases, St. Jude Children's Research Hospital, Mailstop 320 IRC 8057, 332 N. Lauderdale Rd., Memphis, TN 38105, USA.
Fillon
Sophie
S
Smith-Sielicki
S Hope
SH
El Kasmi
Karim C
KC
Gao
Geli
G
Soulis
Konstantinos
K
Patil
Avinash
A
Murray
Peter J
PJ
Tuomanen
Elaine I
EI
D000818:Animals; D002473:Cell Wall / Q000502:physiology*; D005260:Female; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009474:Neurons / Q000473:pathology*; D011008:Pneumococcal Infections / Q000235:genetics / Q000378:metabolism*; D018805:Sepsis / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D013296:Streptococcus pneumoniae / Q000472:pathogenicity*