Gobin Ivana, Susa Milorad, Begic Gabrijela, Hartland Elizabeth L, Doric Miljenko
Department of Microbiology and Parasitology, Medical Faculty, University of Rijeka, B. Branchetta 20, 51000 Rijeka, Croatia.
Department of Microbiology and Immunology, University of Melbourne, Parkville, Victoria 3010, Australia.
J Med Microbiol. 2009 Jun;58(Pt 6):723-730. doi: 10.1099/jmm.0.007476-0.
This study established an experimental model of replicative Legionella longbeachae infection in A/J mice. The animals were infected by intratracheal inoculation of 10(3)-10(9) c.f.u. L. longbeachae serogroup 1 (USA clinical isolates D4968, D4969 and D4973). The inocula of 10(9), 10(8), 10(7) and 10(6) c.f.u. of all tested L. longbeachae serogroup 1 isolates were lethal for A/J mice. Inoculation of 10(5) c.f.u. L. longbeachae caused death in 90 % of the animals within 5 days, whilst inoculation of 10(4) c.f.u. caused sporadic death of mice. All animals that received 10(3) c.f.u. bacteria developed acute lower respiratory disease, but were able to clear Legionella from the lungs within 3 weeks. The kinetics of bacterial growth in the lungs was independent of inoculum size and reached a growth peak about 3 logarithms above the initial inoculum at 72 h after inoculation. The most prominent histological changes in the lungs were observed at 48-72 h after inoculation in the form of a focal, neutrophil-dominant, peribronchiolar infiltration. The inflammatory process did not progress towards the interstitial or alveolar spaces. Immunohistological analyses revealed L. longbeachae serogroup 1 during the early phase of infection near the bronchiolar epithelia and later co-localized with inflammatory cells. BALB/c and C57BL/6 mice strains were also susceptible to infection with all L. longbeachae serogroup 1 strains tested and very similar changes were observed in the lungs of infected animals. These results underline the infection potential of L. longbeachae serogroup 1, which is associated with high morbidity and lethality in mice.
本研究建立了A/J小鼠嗜肺军团菌长滩亚种复制性感染的实验模型。通过气管内接种10³-10⁹ c.f.u.嗜肺军团菌长滩亚种血清型1（美国临床分离株D4968、D4969和D4973）对动物进行感染。所有测试的嗜肺军团菌长滩亚种血清型1分离株的10⁹、10⁸、10⁷和10⁶ c.f.u.接种物对A/J小鼠具有致死性。接种10⁵ c.f.u.嗜肺军团菌长滩亚种导致90%的动物在5天内死亡，而接种10⁴ c.f.u.导致小鼠散发性死亡。所有接受10³ c.f.u.细菌的动物均发生急性下呼吸道疾病，但能够在3周内从肺部清除军团菌。肺部细菌生长动力学与接种量大小无关，接种后72小时达到比初始接种量高约3个对数的生长峰值。接种后48-72小时在肺部观察到最显著的组织学变化，表现为局灶性、以中性粒细胞为主的细支气管周围浸润。炎症过程未向间质或肺泡腔发展。免疫组织学分析显示，在感染早期，嗜肺军团菌长滩亚种血清型1位于细支气管上皮附近，随后与炎症细胞共定位。BALB/c和C57BL/6小鼠品系也对所有测试的嗜肺军团菌长滩亚种血清型1菌株敏感，在感染动物的肺部观察到非常相似的变化。这些结果强调了嗜肺军团菌长滩亚种血清型1的感染潜力，其与小鼠的高发病率和致死率相关。
