A murine model of infection with Rickettsia prowazekii: implications for pathogenesis of epidemic typhus.
Epidemic typhus remains a major disease threat, furthermore, its etiologic agent, Rickettsia prowazekii, is classified as a bioterrorism agent. We describe here a murine model of epidemic typhus that reproduced some features of the human disease. When BALB/c mice were inoculated intravenously with R. prowazekii (Breinl strain), they survived but did not clear R. prowazekii infection. Immunohistological analysis of tissues and quantitative PCR showed that R. prowazekii was present in blood, liver, lungs and brain 1 day after infection and persisted for at least 9 days. Importantly, infected mice developed interstitial pneumonia, with consolidation of the alveoli, hemorrhages in lungs, multifocal granulomas in liver, and hemorrhages in brain, as seen in humans. Circulating antibodies directed against R. prowazekii were detected at day 4 post-infection and steadily increased for up to 21 days, demonstrating that R. prowazekii lesions were independent of humoral immune response. R. prowazekii-induced lesions were associated with inflammatory response, as demonstrated by elevated levels of inflammatory cytokines including interferon-gamma, tumor necrosis factor and the CC chemokine RANTES in the lesions. We concluded that the BALB/c mouse strain provides a useful model for studying the pathogenic mechanisms of epidemic typhus and its control by the immune system.
Bechah
Yassina
Y
Unité des Rickettsies, CNRS UMR 6020, Université de la Méditerranée, Faculté de Médecine, 27 Bld. J. Moulin, 13385 Marseille Cedex 05, France.
Capo
Christian
C
Grau
Georges E
GE
Raoult
Didier
D
Mege
Jean-Louis
JL
D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D018946:Chemokine CCL5 / Q000235:genetics / Q000276:immunology; D004269:DNA, Bacterial / Q000737:chemistry / Q000235:genetics; D004195:Disease Models, Animal; D005260:Female; D007150:Immunohistochemistry; D007371:Interferon-gamma / Q000096:biosynthesis / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D012329:RNA, Bacterial / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012283:Rickettsia prowazekii / Q000235:genetics / Q000254:growth & development*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000235:genetics; D014438:Typhus, Epidemic Louse-Borne / Q000097:blood / Q000382:microbiology*
D000907:Antibodies, Bacterial; D018946:Chemokine CCL5; D004269:DNA, Bacterial; D012329:RNA, Bacterial; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma