Cell wall-mediated neuronal damage in early sepsis

Carlos J. Orihuela; Sophie Fillon; S. Hope Smith-Sielicki; Karim C. El Kasmi; Geli Gao; Konstantinos Soulis; Avinash Patil; Peter J. Murray; Elaine I. Tuomanen

doi:10.1128/IAI.00022-06

Cell wall-mediated neuronal damage in early sepsis

Carlos J. Orihuela, Sophie Fillon, S. Hope Smith-Sielicki, Karim C. El Kasmi, Geli Gao, Konstantinos Soulis, Avinash Patil, Peter J. Murray, Elaine I. Tuomanen

Research output: Contribution to journal › Article › peer-review

36 Scopus citations

Abstract

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.

Original language	English (US)
Pages (from-to)	3783-3789
Number of pages	7
Journal	Infection and immunity
Volume	74
Issue number	7
DOIs	https://doi.org/10.1128/IAI.00022-06
State	Published - Jul 2006
Externally published	Yes

ASJC Scopus subject areas

Parasitology
Microbiology
Immunology
Infectious Diseases

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title = "Cell wall-mediated neuronal damage in early sepsis",

abstract = "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.",

author = "Orihuela, {Carlos J.} and Sophie Fillon and Smith-Sielicki, {S. Hope} and {El Kasmi}, {Karim C.} and Geli Gao and Konstantinos Soulis and Avinash Patil and Murray, {Peter J.} and Tuomanen, {Elaine I.}",

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AU - Orihuela, Carlos J.

AU - Fillon, Sophie

AU - Smith-Sielicki, S. Hope

AU - El Kasmi, Karim C.

AU - Gao, Geli

AU - Soulis, Konstantinos

AU - Patil, Avinash

AU - Murray, Peter J.

AU - Tuomanen, Elaine I.

PY - 2006/7

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N2 - 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.

AB - 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.

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Cell wall-mediated neuronal damage in early sepsis

Abstract

ASJC Scopus subject areas

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