Mouse models of aerosol-acquired tularemia caused by Francisella tularensis types A and B.
After preliminary assessment of virulence in AKR/J, DBA/1, BALB/c, and C57BL/6 mice, we investigated histopathologic changes in BALB/c and C57BL/6 mice infected with type A (strain SCHU S4) or type B (strain 425) Francisella tularensis by aerosol exposure. In mice exposed to type A infection, changes in histologic presentation were not apparent until day 3 after infection, when pyogranulomatous inflammation was detected in spleens and livers of BALB/c mice, and in lungs and spleens of C57BL/6 mice. Histopathologic changes were most severe and widespread in both mouse strains on day 5 after infection and seemed to completely resolve within 22 d of challenge. BALB/c mice were more resistant than C57BL/6 mice in lethal-dose calculations, but C57BL/6 mice cleared the infection more rapidly. Mice similarly challenged with type B F. tularensis also developed histopathologic signs of infection beginning on day 3. The most severe changes were noted on day 8 and were characterized by granulomatous or pyogranulomatous infiltrations of the lungs. Unlike type A infection, lesions due to type B did not resolve over time and remained 3 wk after infection. In type B, but not type A, infection we noted extensive inflammation of the heart muscle. Although no microorganisms were found in tissues of type A survivors beyond 9 d after infection, mice surviving strain 425 infection had a low level of residual infection at 3 wk after challenge. The histopathologic presentation of tularemia caused by F. tularensis types A and B in BALB/c and C57BL/6 mice bears distinct similarities to tularemia in humans.
Bacteriology Division, U.S. Army Medical Research Institute of Infectious Diseases, Fort Detrick, Maryland, USA.
David L
DL
Fritz
Bacteriology Division, U.S. Army Medical Research Institute of Infectious Diseases, Fort Detrick, Maryland, USA.
Marilyn J
MJ
England
Bacteriology Division, U.S. Army Medical Research Institute of Infectious Diseases, Fort Detrick, Maryland.
Lynda
L
Miller
Bacteriology Division, U.S. Army Medical Research Institute of Infectious Diseases, Fort Detrick, Maryland, USA. david.m.waag.ctr@mail.mil.
David M
DM
Waag
D000336:Aerosols / Q000008:administration & dosage; D000818:Animals; D004195:Disease Models, Animal; D005604:Francisella tularensis / Q000145:classification / Q000235:genetics*; D007249:Inflammation / Q000382:microbiology / Q000473:pathology*; D008099:Liver / Q000473:pathology; D008168:Lung / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C / Q000276:immunology* / Q000382:microbiology; D008810:Mice, Inbred C57BL / Q000276:immunology* / Q000382:microbiology; D013045:Species Specificity; D013154:Spleen / Q000473:pathology; D014406:Tularemia / Q000276:immunology / Q000382:microbiology* / Q000503:physiopathology*
D000336:Aerosols