| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2006: ¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 2005: ¥2,000,000 (Direct Cost: ¥2,000,000)
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| Research Abstract |
Listeria monocytogenes is a gram-positive bacterium that causes meningitis and febrile gastroenteritis. The outcome of listeriosis is dependent on host factors such as age, pregnancy, and HIV infection, which influence host immunocompetency. A Th-1 type cytokine IFN-γ plays an important role in the innate immune response against intracellular bacterial pathogens. In contrast, Th2-biased immune responses often associate with most atopic diseases. NC/Nga is a model mouse for human atopic dermatitis (AD). Having a genetic predisposition to AD, since they spontaneously develop AD-like skin lesion under conventional environment, but not under SPF conditions. In this study, we examined whether atopic predisposition affected the immune response to L. monocytogenes infection.
We used NC/Nga that did not develop any skin lesions, and compared their susceptibility to L. monocytogenes infection with BALB/c and C57BL/6 mice. NC/Nga were highly susceptible to L. monocytogenes infection : the 50% lethal dose was significantly lower and the number of bacteria in livers, spleens and brains were higher in NC/Nga than those for other inbred mice. The breakdown of blood-brain barrier in NC/Nga brains was observed at 3 days post infection, but not in BALB/c and C57BL/6. As compared to BALB/c and C57BL/6 mice, plasma IFN-γ levels of NC/Nga were comparative. In contrast, markedly increased plasma IL-10 levels were detected in NC/Nga in the early course of infection. Blockade of IL-10 exacerbated the symptoms and increased susceptibility to the infection. Treatment with IL-10 increased survival rate. Yet the molecular mechanisms by which L. monocytogenes stimulates overproduction of IL-10 in NC/Nga mice remain unknown, our results suggest that atopic predisposition may associate with the differential immune responses to the pathogen and higher susceptibility to L. monocytogenes in NC/Nga mice. Our study implies an atopic phenotype may one of the potential risk factors for the infection.
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