Genetic identification of unique immunological responses in mice infected with virulent and attenuated Francisella tularensis.
Francisella tularensis is a category A select agent based on its infectivity and virulence but disease mechanisms in infection remain poorly understood. Murine pulmonary models of infection were therefore employed to assess and compare dissemination and pathology and to elucidate the host immune response to infection with the highly virulent Type A F. tularensis strain Schu4 versus the less virulent Type B live vaccine strain (LVS). We found that dissemination and pathology in the spleen was significantly greater in mice infected with F. tularensis Schu4 compared to mice infected with F. tularensis LVS. Using gene expression profiling to compare the response to infection with the two F. tularensis strains, we found that there were significant differences in the expression of genes involved in the apoptosis pathway, antigen processing and presentation pathways, and inflammatory response pathways in mice infected with Schu4 when compared to LVS. These transcriptional differences coincided with marked differences in dissemination and severity of organ lesions in mice infected with the Schu4 and LVS strains. Therefore, these findings indicate that altered apoptosis, antigen presentation and production of inflammatory mediators explain the differences in pathogenicity of F. tularensis Schu4 and LVS.
Rocky Mountain Regional Center of Excellence, Colorado State University, Fort Collins, CO 80523, USA.
Luke C
LC
Kingry
Ryan M
RM
Troyer
Nicole L
NL
Marlenee
Helle
H
Bielefeldt-Ohmann
Richard A
RA
Bowen
Alan R
AR
Schenkel
Steven W
SW
Dow
Richard A
RA
Slayden
D000818:Animals; D017209:Apoptosis; D004195:Disease Models, Animal; D005260:Female; D005604:Francisella tularensis / Q000472:pathogenicity*; D020869:Gene Expression Profiling / Q000379:methods; D006651:Histocytochemistry; D054884:Host-Pathogen Interactions; D008168:Lung / Q000382:microbiology; D051379:Mice; D008810:Mice, Inbred C57BL; D020411:Oligonucleotide Array Sequence Analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013154:Spleen / Q000382:microbiology; D014406:Tularemia / Q000235:genetics* / Q000276:immunology* / Q000382:microbiology; D014774:Virulence