immune system
N |
• mice exhibit normal immune system development, with no significant alterations in the numbers and percentages of B and T lymphocytes and myeloid cells in primary and secondary lymphoid organs relative to wild-type controls
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• at 65 h post-infection with Listeria monocytogenes, mice show a significantly higher serum IL-12 p40 level than similarly infected wild-type controls
• however, no differences in bacterial burden are observed in spleen or liver at 65 h post-infection
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• at 36 h post-infection with Listeria monocytogenes, mice show a significantly higher serum TNF-alpha level than similarly infected wild-type controls
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• after stimulation with LPS and IFN-gamma, bone-marrow-derived dendritic cells (BMDCs) produce significantly more IL-12 p40 relative to wild-type BMDCs
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• after stimulation with LPS and IFN-gamma, BMDCs produce significantly more IL-6 relative to wild-type BMDCs
• pretreatment of BMDCs with tert-butylhydroquinone (tBHQ) reduces IL-6 production, unlike in wild-type BMDCs
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• after stimulation with LPS and IFN-gamma, BMDCs produce significantly more TNF-alpha relative to wild-type BMDCs
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homeostasis/metabolism
• at 65 h post-infection with Listeria monocytogenes, mice show a significantly higher serum IL-12 p40 level than similarly infected wild-type controls
• however, no differences in bacterial burden are observed in spleen or liver at 65 h post-infection
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• at 36 h post-infection with Listeria monocytogenes, mice show a significantly higher serum TNF-alpha level than similarly infected wild-type controls
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• after stimulation with LPS and IFN-gamma, BMDCs produce significantly higher levels of nitrite relative to wild-type BMDCs, indicating increased reactive nitrogen intermediate (RNI) synthesis
• however, pretreatment of BMDCs with tert-butylhydroquinone (tBHQ, an electrophile that induces the antioxidant response) reduces NO production in stimulated BMDCs, as seen in wild-type BMDCs
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• BMDCs exhibit a reduced basal oxygen consumption rate (OCR) and a corresponding reduction in maximal respiration rate
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cellular
• BMDCs exhibit a reduced basal oxygen consumption rate (OCR) and a corresponding reduction in maximal respiration rate
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• BMDCs show reduced levels of cellular ATP corresponding to decreased mitochondrial respiration
• however, glycolysis and fatty acid oxidation are normal
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• BMDCs show lower mitochondrial reactive oxygen species (mROS) production both at basal state and after stimulation with LPS and IFN-gamma, as determined by MitoSOX, a superoxide-specific fluorescent probe that localizes to mitochondria
• however, unstimulated BMDCs show normal cellular redox states as determined by DCFDA, a redox-sensitive probe that detects several reactive oxygen and nitrogen intermediates
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• after stimulation with LPS and IFN-gamma, BMDCs show an elevated cellular oxidative state relative to wild-type BMDCs, as determined by DCFDA
• increase in oxidative stress is reduced to wild-type levels after iNOS inhibition with 1400W pretreatment, indicating that reactive nitrogen intermediate (RNI) production underlies the increase in overall oxidative stress in stimulated BMDCs
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