Cholinergic stimulation of the immune system protects against lethal infection by Salmonella enterica serovar Typhimurium.
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Cholinergic stimulation of the immune system protects against lethal infection by Salmonella enterica serovar Typhimurium. / Fernandez-Cabezudo, Maria J; Lorke, Dietrich; Azimullah, Sheikh; Mechkarska, Milena; Hasan, Mohammed Y; Petroianu, Georg A; Al-Ramadi, Basel K.
in: IMMUNOLOGY, Jahrgang 130, Nr. 3, 3, 2010, S. 388-398.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Cholinergic stimulation of the immune system protects against lethal infection by Salmonella enterica serovar Typhimurium.
AU - Fernandez-Cabezudo, Maria J
AU - Lorke, Dietrich
AU - Azimullah, Sheikh
AU - Mechkarska, Milena
AU - Hasan, Mohammed Y
AU - Petroianu, Georg A
AU - Al-Ramadi, Basel K
PY - 2010
Y1 - 2010
N2 - SUMMARY: The cholinergic nervous system has been demonstrated to attenuate the inflammatory response during sepsis via the inhibitory action of acetylcholine (ACh) on macrophages. These findings were largely based on experimental sepsis models using endotoxin as the inducing agent. Herein, however, we report that the specific inhibition of acetylcholinesterase (AChE) renders animals more resistant to infection by a virulent strain of Salmonella enterica serovar Typhimurium, a Gram-negative enteric pathogen. Inhibition of AChE was induced by a subchronic exposure to paraoxon, a potent anti-cholinesterase metabolite of the organophosphorous compound parathion. Our findings indicate that inhibition of AChE enhanced survival of infected mice in a dose-dependent fashion and this correlated with efficient control of bacterial proliferation in target organs. Immunologically, inhibition of AChE enabled the animals to mount a more effective inflammatory anti-microbial response, and to secrete higher levels of interleukin-12, a key T helper type 1-promoting cytokine. The ACh-induced enhancement in resistance to infection was abrogated by co-administration of an oxime which can reactivate AChE. Hence, in a model of Gram-negative bacterial infection, cholinergic stimulation is shown to enhance the anti-microbial immune response leading to effective control of bacterial proliferation and enhanced animal survival.
AB - SUMMARY: The cholinergic nervous system has been demonstrated to attenuate the inflammatory response during sepsis via the inhibitory action of acetylcholine (ACh) on macrophages. These findings were largely based on experimental sepsis models using endotoxin as the inducing agent. Herein, however, we report that the specific inhibition of acetylcholinesterase (AChE) renders animals more resistant to infection by a virulent strain of Salmonella enterica serovar Typhimurium, a Gram-negative enteric pathogen. Inhibition of AChE was induced by a subchronic exposure to paraoxon, a potent anti-cholinesterase metabolite of the organophosphorous compound parathion. Our findings indicate that inhibition of AChE enhanced survival of infected mice in a dose-dependent fashion and this correlated with efficient control of bacterial proliferation in target organs. Immunologically, inhibition of AChE enabled the animals to mount a more effective inflammatory anti-microbial response, and to secrete higher levels of interleukin-12, a key T helper type 1-promoting cytokine. The ACh-induced enhancement in resistance to infection was abrogated by co-administration of an oxime which can reactivate AChE. Hence, in a model of Gram-negative bacterial infection, cholinergic stimulation is shown to enhance the anti-microbial immune response leading to effective control of bacterial proliferation and enhanced animal survival.
KW - Animals
KW - Male
KW - Survival Analysis
KW - Mice
KW - Mice, Inbred BALB C
KW - Nitric Oxide metabolism
KW - Cytokines blood
KW - Cell Count
KW - Macrophages cytology
KW - Acetylcholinesterase metabolism
KW - B-Lymphocytes cytology
KW - Cholinesterase Inhibitors pharmacology
KW - Cholinesterase Reactivators pharmacology
KW - Concanavalin A pharmacology
KW - Erythrocytes drug effects
KW - GPI-Linked Proteins
KW - Immune System drug effects
KW - Lipopolysaccharides pharmacology
KW - Lymph Nodes microbiology
KW - Oximes pharmacology
KW - Paraoxon pharmacology
KW - Pyridinium Compounds pharmacology
KW - Salmonella Infections blood
KW - Salmonella typhimurium pathogenicity
KW - Spleen cytology
KW - T-Lymphocytes cytology
KW - Thymus Gland drug effects
KW - Animals
KW - Male
KW - Survival Analysis
KW - Mice
KW - Mice, Inbred BALB C
KW - Nitric Oxide metabolism
KW - Cytokines blood
KW - Cell Count
KW - Macrophages cytology
KW - Acetylcholinesterase metabolism
KW - B-Lymphocytes cytology
KW - Cholinesterase Inhibitors pharmacology
KW - Cholinesterase Reactivators pharmacology
KW - Concanavalin A pharmacology
KW - Erythrocytes drug effects
KW - GPI-Linked Proteins
KW - Immune System drug effects
KW - Lipopolysaccharides pharmacology
KW - Lymph Nodes microbiology
KW - Oximes pharmacology
KW - Paraoxon pharmacology
KW - Pyridinium Compounds pharmacology
KW - Salmonella Infections blood
KW - Salmonella typhimurium pathogenicity
KW - Spleen cytology
KW - T-Lymphocytes cytology
KW - Thymus Gland drug effects
M3 - SCORING: Zeitschriftenaufsatz
VL - 130
SP - 388
EP - 398
JO - IMMUNOLOGY
JF - IMMUNOLOGY
SN - 0019-2805
IS - 3
M1 - 3
ER -