Abstract
BackgroundPneumonia and pulmonary infections are major causes of mortality among the growing elderly population. Age associated attenuations of various immune parameters, involved with both innate and adaptive responses are collectively known as immune senescence. These changes are likely to be involved with differences in host susceptibility to disease between young and aged individuals.Methodology/Principal FindingsThe objective of this study was to assess potential age related differences in the pulmonary host response in mice to the Gram-negative respiratory pathogen, Francisella novicida. We intranasally infected mice with F. novicida and compared various immune and pathological parameters of the pulmonary host response in both young and aged mice.Conclusions/SignificanceWe observed that 20% of aged mice were able to survive an intranasal challenge with F. novicida while all of their younger cohorts died consistently within 4 to 6 days post infection. Further experiments revealed that all of the aged mice tested were initially able to control bacterial replication in the lungs as well as at distal sites of replication compared with young mice. In addition, the small cohort of aged survivors did not progress to a severe sepsis syndrome with hypercytokinemia, as did all of the young adult mice. Finally, a lack of widespread cell death in potential aged survivors coupled with a difference in cell types recruited to sites of infection within the lung confirmed an altered host response to Francisella in aged mice.
Highlights
Infectious diseases including pneumonia, bacteremia, and influenza remain among the top ten causes of morbidity and mortality among the elderly [1]
Direct evidence ascertaining the relationship between age and infection with Francisella in humans is difficult to interpret as some studies indicated a positive correlation between Francisella infection and age and others a negative one [23,24,25]
Studies from our lab have indicated that the route of infection with Francisella is an important determinant of bacterial dissemination as well as disease progression and outcome [26]
Summary
Infectious diseases including pneumonia, bacteremia, and influenza remain among the top ten causes of morbidity and mortality among the elderly [1]. The immune system undergoes numerous changes that may affect our susceptibility to infection. Changes with regard to components of cell mediated immunity and humoral immunity have all been reported to fluctuate with respect to age [2,3,4]. Components of the innate immune system have been reported to undergo modifications with regard to age. Pneumonia and pulmonary infections are major causes of mortality among the growing elderly population. Age associated attenuations of various immune parameters, involved with both innate and adaptive responses are collectively known as immune senescence. These changes are likely to be involved with differences in host susceptibility to disease between young and aged individuals
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