Molecular immunology of experimental primary tularemia in mice infected by respiratory or intradermal routes with type A Francisella tularensis
| Autor: | Gregory Harris, Mark Bolanowski, Wangxue Chen, J. Wayne Conlan, Anders Sjöstedt, Cecilia Rietz, Hua Shen, Xigeng Zhao |
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| Rok vydání: | 2008 |
| Předmět: |
Chemokine
potential isolation & purification Respiratory System state Tularemia Mice site pathogenicity genetics bacteria Francisella tularensis Pathogen Mice Inbred BALB C united states food and drug administration biology pathogenesis Dermis vaccines Liver Female Chemokines Canada Immunology Virulence restricted Article lung Proinflammatory cytokine strain Immune system blood medicine Animals bacterial molecular RNA Messenger Molecular Biology Aerosols disease united states Intracellular parasite microbiology medicine.disease biology.organism_classification cytokines infection Mice Inbred C57BL Kinetics Gene Expression Regulation growth & development biology.protein RNA metabolism serum Spleen |
| Zdroj: | Molecular Immunology. 45:2962-2969 |
| ISSN: | 0161-5890 |
| Popis: | The type A subspecies of Francisella tularensis is a highly virulent facultative intracellular bacterial pathogen, and a potential biological weapon. Recently, there has been renewed interest in developing new vaccines and therapeutics against this bacterium. Natural cases of disease, tularemia, caused by the type A subspecies are very rare. Therefore, the United States Food and Drug Administration will rely on the so-called Animal Rule for efficacy testing of anti-Francisella medicines. This requires the human disease to be modeled in one or more animal species in which the pathogenicity of the agent is reasonably well understood. Mice are natural hosts for F. tularensis, and might be able to satisfy this requirement. Tularemia pathogenesis appears to be primarily due to the host inflammatory response which is poorly understood at the molecular level. Additionally, the extent to which this response varies depending on host and pathogen genetic background, or by pathogen challenge route or dose is unknown. Therefore, the present study examined sera and infected tissues from C57BL/6 and BALB/c mice challenged by natural intradermal (ID) and respiratory routes with one of two distinct type A strains of the pathogen for cytokine and chemokine responses that might help to explain the morbidity associated with tularemia. The results show that the molecular immune response was mostly similar regardless of the variables examined. For instance, mRNA for the proinflammatory cytokine IL-6, and chemokines KC, and IP-10 was consistently upregulated at all sites of infection. Upregulation of mRNA for several other cytokines and chemokines occurred in a more tissue restricted manner. For instance, IFN-gamma was highly upregulated in the skin of BALB/c, but not C57BL/6 mice after ID inoculation of the pathogen, whilst IL-10 mRNA upregulation was only consistently seen in the skin and lungs. |
| Databáze: | OpenAIRE |
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