Experimental tularemia in mice challenged by aerosol or intradermally with virulent strains of Francisella tularensis: bacteriologic and histopathologic studies

Conlan, J. Wayne; Chen, Wangxue; Shen, Hua; Webb, Ann; KuoLee, Rhonda

doi:10.1016/s0882-4010(03)00046-9

Cited by 155 publications

(219 citation statements)

References 27 publications

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“…route. As expected from our previous work [13,21], all shamimmunized mice died after challenge with the highly virulent type A strain by day 6 and the less virulent type B strain between days 7 and 8. In contrast, all LVS-immunized mice survived the challenge except one mouse that died on day 6 or 10, respectively, after i.d.…”

Section: Oral Lvs Immunization Protects Balb/c Mice Against Type a Ansupporting

confidence: 87%

“…or i.d route with various strains of F. tularensis in 50 μl PBS. Actual concentrations of the inoculum in each experiment were determined by plating 10-fold serial dilutions on cystine heart agar supplemented with 1% (w/v) hemoglobin [21]. In some experiments, mice were challenged by aerosol with type A F. tularensis, as described previously [21].…”

Section: Immunization Of Mice and Challenge With F Tularensismentioning

confidence: 99%

“…Actual concentrations of the inoculum in each experiment were determined by plating 10-fold serial dilutions on cystine heart agar supplemented with 1% (w/v) hemoglobin [21]. In some experiments, mice were challenged by aerosol with type A F. tularensis, as described previously [21]. Briefly, low-dose aerosols of F. tularensis were generated with a Lovelace nebulizer and a customized commercial nose-only exposure apparatus (In-tox Products, Albuquerque, NM), which delivered an initial retained dose of approximately 20 cfu F. tularensis into the lungs [21].…”

Section: Immunization Of Mice and Challenge With F Tularensismentioning

confidence: 99%

“…The tissues were cut into small pieces and homogenized using an aerosol-proof homogenizer. Ten-fold serial dilutions of the tissue homogenates were plated on cystine heart agar supplemented with 1% (w/v) hemoglobin and sulfamethoxazole and trimethoprim [21]. Colonies were counted after 72 hours of incubation at 37°C.…”

Section: Quantitative Bacteriology and Histopathologymentioning

confidence: 99%

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Oral immunization of mice with the live vaccine strain (LVS) of Francisella tularensis protects mice against respiratory challenge with virulent type A F. tularensis

KuoLee

Harris

Conlan

et al. 2007

Vaccine

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Francisella tularensis is a gram-negative intracellular bacterium, and the causative agent of tularemia. The infection can be initiated by various routes and can manifest itself in several clinical forms with the disseminated typhoidal form initiated by inhalation being most fatal. The attenuated live vaccine strain (LVS), developed almost 50 years ago, remains the sole effective tularemia vaccine, which is still only available as an Investigational New Drug for at-risk individuals. This vaccine, when given by scarification, appears to provide solid protection against subsequent systemic infection with clinical strains of F. tularensis, but its efficacy against respiratory infection is less satisfactory. In this study, we evaluated the potential of oral immunization with LVS for eliciting protection against systemic and respiratory infection with virulent F. tularensis strains in a mouse model of tularemia. Oral LVS immunization was highly effective at protecting Balb/c mice against lethal systemic or respiratory challenges with type A and type B F. tularensis. Compared to shamimmunized mice, oral LVS-immunized mice showed significant reductions in burdens of virulent F. tularensis in the lung and spleen and milder tissue damage and inflammation in the liver. The immunization induced F. tularensis -specific antibody responses in the serum and bronchoalveolar lavage fluids, as well as antigen-specific splenocyte proliferation and IFN-γ and IL-2 production. The protective efficacy was related to the size of the immunizing dose but not the number of doses administered. Like other routes of LVS immunization in mice, the protective immunity induced by oral immunization was relatively short-lived. These results suggest that oral immunization should be explored further as an alternative vaccination strategy to combat tularemia.

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Section: Oral Lvs Immunization Protects Balb/c Mice Against Type a Ansupporting

confidence: 87%

Section: Immunization Of Mice and Challenge With F Tularensismentioning

confidence: 99%

Section: Immunization Of Mice and Challenge With F Tularensismentioning

confidence: 99%

Section: Quantitative Bacteriology and Histopathologymentioning

confidence: 99%

See 2 more Smart Citations

Oral immunization of mice with the live vaccine strain (LVS) of Francisella tularensis protects mice against respiratory challenge with virulent type A F. tularensis

KuoLee

Harris

Conlan

et al. 2007

Vaccine

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“…37 Our present findings indicate that many of the genes prominently upregulated during the early phase of human tularemia are also dependent on IFN-g for their expression. Previous studies have demonstrated that a protective, cell-mediated immune response develops during the second week of infection.…”

Section: Transcriptional Host Response During Tularemia H Andersson Esupporting

confidence: 56%

Transcriptional profiling of the peripheral blood response during tularemia

et al. 2006

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Tularemia is a febrile disease caused by the highly contagious bacterium Francisella tularensis. We undertook an analysis of the transcriptional response in peripheral blood during the course of ulceroglandular tularemia by use of Affymetrix microarrays comprising 14 500 genes. Samples were obtained from seven individuals at five occasions during 2 weeks after the first hospital visit and convalescent samples 3 months later. In total, 265 genes were differentially expressed, 95 of which at more than one time point. The differential expression was verified with real-time quantitative polymerase chain reaction for 36 genes (R 2 ¼ 0.590). The most prominent changes were noted in samples drawn on days 2-3 and a considerable proportion of the upregulated genes appeared to represent an interferon-g-induced response and also a proapoptotic response. Genes involved in the generation of innate and acquired immune responses were found to be downregulated, presumably a pathogen-induced event. A logistic regression analysis revealed that seven genes were good predictors of the early phase of tularemia. This is the first description of the transcriptional host response to ulceroglandular tularemia and the study has identified gene subsets relevant to the pathogenesis of the disease and subsets that may serve as early diagnostic biomarkers.

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Infection of Mice with Francisella as an Immunological Model

et al. 2011

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This unit describes the utility of various mouse models of infection for studying pathogenesis and adaptive immune responses to the facultative intracellular bacteria pathogen Francisella tularensis. By judicious use of different combinations of mouse and bacterial strains, as well as different routes of infection, murine tularemia models may be used to explore a complete picture of F. tularensis infection and immunity. Moreover, studies using Francisella, particularly the Live Vaccine Strain (LVS), serve as a convenient and tractable model system that appears to be representative of mammalian host responses to intracellular pathogens in general.

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Experimental tularemia in mice challenged by aerosol or intradermally with virulent strains of Francisella tularensis: bacteriologic and histopathologic studies

Cited by 155 publications

References 27 publications

Oral immunization of mice with the live vaccine strain (LVS) of Francisella tularensis protects mice against respiratory challenge with virulent type A F. tularensis

Oral immunization of mice with the live vaccine strain (LVS) of Francisella tularensis protects mice against respiratory challenge with virulent type A F. tularensis

Transcriptional profiling of the peripheral blood response during tularemia

Infection of Mice with Francisella as an Immunological Model

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