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Mentions: We intranasally infected both young (8–12 week old) and aged mice (22–24 month old) with F. novicida with 4–9×102 CFU/20 µL. In our laboratory a dose of about 3×102 CFU/20 µL is sufficient to cause mortality in 100% of young mice within 4 to 6 days post infection. After infection, we monitored the mice of each age group for the next 16 days (Fig. 1). Initially we noticed that young mice were exhibiting several symptoms including hunched posture, piloerection, lethargy and in severe cases eye discharge beginning on day 3 post infection. These symptoms persisted and worsened in the young animals, and all of them died between 4 and 6 days post infection (n = 18). Symptoms in the aged group were difficult to detect at 3 DPI as this age group appeared similar to mock-infected aged mice and were still quite active. However, the symptoms that were evident in the young mice at 3 DPI began to appear at 4 DPI in the infected aged mice, and most aged mice succumbed to infection between days 5 and 6 post infection. However, a small, but significant proportion survived until day 8 post infection and continued to survive or seemingly cleared the infection by day 16 post infection (4/18; p = .0002).
Attenuated Response of Aged Mice to Respiratory Francisella novicida Is Characterized by Reduced Cell Death and Absence of Subsequent Hypercytokinemia
Bottom Line: 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.
Affiliation: Department of Microbiology and Immunology, The University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA.
Abstract: 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.The 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.We 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.
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