Attenuated response of aged mice to respiratory Francisella novicida is characterized by reduced cell death and absence of subsequent hypercytokinemia.
BACKGROUND
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.


RESULTS
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.


CONCLUSIONS
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.
Department of Microbiology and Immunology, The University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA.
Chris A
CA
Mares
Jyotika
J
Sharma
Sandra S
SS
Ojeda
Qun
Q
Li
Jocelyn A
JA
Campos
Elizabeth G
EG
Morris
Jacqueline J
JJ
Coalson
Judy M
JM
Teale
D000375:Aging / Q000276:immunology*; D000818:Animals; D017209:Apoptosis / Q000276:immunology; D002470:Cell Survival / Q000276:immunology; D016207:Cytokines / Q000097:blood / Q000276:immunology; D005260:Female; D005603:Francisella / Q000276:immunology* / Q000502:physiology; D016905:Gram-Negative Bacterial Infections / Q000276:immunology* / Q000382:microbiology; D054884:Host-Pathogen Interactions / Q000276:immunology; D018836:Inflammation Mediators / Q000097:blood / Q000276:immunology; D053208:Kaplan-Meier Estimate; D008168:Lung / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D008171:Lung Diseases / Q000276:immunology* / Q000382:microbiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008856:Microscopy, Fluorescence
D016207:Cytokines; D018836:Inflammation Mediators