Francisella tularensis is the causative agent of tularemia. It is an intracellular pathogen with the ability to survive within phagosomes and induce pyroptotic cell death. In this study, we attempted to prove whether oxidative imbalance plays a significant role in tularemia pathogenesis. In our experimental model, we subcutaneously infected female BALB/c mice (dose 10(5) CFU of F. tularensis LVS). Liver, spleen, and blood were collected from mice at regular intervals from days 1-15 after infection. The bacterial burden was assessed by a cultivation test. The burden was unchanging from the 2(nd) to 6(th) day after infection. The bacterial burden corresponded to the plasmatic level of IFN-γ, IL-6, and liver malondialdehyde. After the phase of acute bacteraemia and the innate immunity reaction, the levels of reduced glutathione and total low molecular weight antioxidants decreased significantly and the activity of caspase-3 increased in the liver. The level of reduced glutathione decreased to 25% of the original level, and the total level of low molecular weight antioxidants was less than 50% of the initial amount. The demonstrated effects of tularemia-induced pathology had a more extensive impact on the liver than on the spleen.

• MeSH
• Antioxidants analysis   MeSH
• Bacterial Load MeSH
• Francisella tularensis pathogenicity   MeSH
• Interferon-gamma blood   MeSH
• Interleukin-6 blood   MeSH
• Liver microbiology   MeSH
• Blood microbiology   MeSH
• Malondialdehyde analysis   MeSH
• Disease Models, Animal MeSH
• Mice, Inbred BALB C MeSH
• Mice MeSH
• Oxidative Stress * MeSH
• Spleen microbiology   MeSH
• Tularemia microbiology   pathology   MeSH
• Animals MeSH
• Check Tag
• Mice MeSH
• Female MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Antioxidants MeSH
• Interferon-gamma MeSH
• Interleukin-6 MeSH
• Malondialdehyde MeSH

The present experiment was aimed at assessing the application of neostigmine, an acetylcholinesterase (AChE) pseudo-irreversible inhibitor with poor penetration through the hematoencephalitic barrier, and the neurotransmitter acetylcholine (ACh). The experiment was done to evaluate their ability to modulate an infectious disease: tularemia. Mice infected with Franciselle tularensis and exposed to either ACh or neostigmine had a higher mortality and spleen bacterial burden when compared to infected mice exposed to saline solution only. The activated cholinergic anti-inflammatory pathway suppressed pathways necessary for tularemia resolution. Administration of AChE inhibitors to the individuals suffering from tularemia is contra-indicatory. Drugs based on AChE inhibition should be restricted when tularemia or disease with a similar pathogenesis is suspected.

• Keywords
• Francisella tularensis, cholinergic anti-inflammatory pathway, cholinergic system, immunomodulation, intracellular pathogen, parasympathicus,
• Publication type
• Journal Article MeSH