The Journal of infectious diseases
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Preclinical evaluation of tuberculosis drugs is generally limited to mice. However, necrosis and hypoxia, key features of human tuberculosis lesions, are lacking in conventional mouse strains. ⋯ We demonstrate that tuberculosis lesions in C3HeB/FeJ are hypoxic. Activities of some key tuberculosis drug regimens in development are represented differently in C3HeB/FeJ versus BALB/c mice. Because C3HeB/FeJ display key features of human tuberculosis, this strain warrants evaluation as a more pathologically relevant model for preclinical studies.
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Growing evidence indicates that influenza pathogenicity relates to altered immune responses and hypercytokinemia. Therefore, dampening the excessive inflammatory response induced after infection might reduce influenza morbidity and mortality. ⋯ Our results demonstrate for the first time that treatment of mice with 15d-PGJ(2) reduces influenza morbidity and mortality through activation of the PPARγ pathway. PPARγ agonists could thus represent a potential therapeutic avenue for influenza infections.
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Sepsis is associated with mitochondrial dysfunction and impaired oxygen consumption, which may condition clinical outcome independent of tissue oxygenation. However, mitochondrial role in sepsis severity remains unknown. We aimed to characterize mitochondrial function in sepsis, establish its origin and cellular consequences, and determine its correlation with clinical symptoms and outcome. ⋯ A plasmatic factor such as nitric oxide, increased in inflammation and able to induce mitochondrial dysfunction, oxidative stress and apoptosis, may be responsible for cell damage in sepsis. Together with bacterial infection, leakage of mitochondrial DNA from damaged cells into circulation could contribute to systemic inflammatory response syndrome. Mitochondrial dysfunction and inflammation correlate with sepsis severity and outcome, becoming targets for supporting therapies.
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Obesity, a risk factor for increased severity of diverse diseases, is believed to have negative impact on vaccine efficacy. Recently, mortality has emerged as an outcome of pandemic influenza A virus subtype H1N1, necessitating development of effective vaccine strategies. Here we investigated effects of diet-induced obesity on vaccine-induced immune responses and protective efficacy against pandemic H1N1 influenza virus. ⋯ Our results show that prophylactic immune responses and protectiveness induced by 2009 H1N1 vaccine could be extremely compromised in diet-induced obesity. These results suggest that novel vaccination strategies for high-risk groups, including the obese population, are required.