Intravenous infection of virulent shigellae causes fulminant hepatitis in mice.
Shigella spp. are pathogenic bacteria responsible for bacillary dysentery in humans. The major lesions in colonic mucosa are intense inflammation with apoptosis of macrophages and release of pro-inflammatory cytokines. The study of shigellosis is hindered by the natural resistance of rodents to oral infection with Shigella. Therefore, animal models exploit other routes of infection. Here, we describe a novel murine model in which animals receive shigellae via the caudal vein. Mice infected with 5 x 10(6) (LD(50)) virulent shigellae died at 48 h post infection, whereas animals receiving non-invasive mutants survived. The liver is the main target of infection, where shigellae induce microgranuloma formation. In mice infected with invasive bacteria, high frequency of apoptotic cells is observed within hepatic microgranulomas along with significant levels of mRNA for pro-inflammatory cytokines such as IL-1beta, IL-18, IL-12 and IFN-gamma. Moreover, in the blood of these animals high levels of IL-6 and transaminases are detected. Our results demonstrate the intravenous model is suitable for pathogenicity studies and useful to explore the immune response after Shigella infection.
Martino
Maria Celeste
MC
Dipartimento di Biologia Cellulare e dello Sviluppo, Sezione di Scienze Microbiologiche, Università 'La Sapienza', Via dei Sardi 70, 00185 Roma, Italy.
Rossi
Giacomo
G
Tattoli
Ivan
I
Martini
Irene
I
Chiavolini
Damiana
D
Cortese
Giancarlo
G
Pozzi
Gianni
G
Bernardini
Maria Lina
ML
D000818:Animals; D017209:Apoptosis; D015169:Colony Count, Microbial; D004195:Disease Models, Animal; D004405:Dysentery, Bacillary / Q000382:microbiology*; D005260:Female; D006099:Granuloma / Q000382:microbiology / Q000473:pathology; D006505:Hepatitis / Q000382:microbiology* / Q000473:pathology; D022781:Hepatocytes / Q000378:metabolism; D007371:Interferon-gamma / Q000235:genetics; D007375:Interleukin-1 / Q000235:genetics; D018664:Interleukin-12 / Q000235:genetics; D020382:Interleukin-18 / Q000096:biosynthesis / Q000235:genetics; D053583:Interleukin-1beta; D015850:Interleukin-6 / Q000097:blood; D008099:Liver / Q000382:microbiology / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D010446:Peptide Fragments / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D012760:Shigella / Q000276:immunology / Q000472:pathogenicity*; D000637:Transaminases / Q000097:blood; D014774:Virulence
D007375:Interleukin-1; D020382:Interleukin-18; D053583:Interleukin-1beta; D015850:Interleukin-6; D010446:Peptide Fragments; D012333:RNA, Messenger; C052994:interleukin-1beta (163-171); D018664:Interleukin-12; D007371:Interferon-gamma; D000637:Transaminases