| Autor: |
Huang MT; Department of Microbiology and Immunology, University of North Carolina, Chapel Hill, NC 27599-7290, USA., Mortensen BL, Taxman DJ, Craven RR, Taft-Benz S, Kijek TM, Fuller JR, Davis BK, Allen IC, Brickey WJ, Gris D, Wen H, Kawula TH, Ting JP |
| Jazyk: |
angličtina |
| Zdroj: |
Journal of immunology (Baltimore, Md. : 1950) [J Immunol] 2010 Nov 01; Vol. 185 (9), pp. 5476-85. Date of Electronic Publication: 2010 Oct 04. |
| DOI: |
10.4049/jimmunol.1002154 |
| Abstrakt: |
Francisella tularensis is a facultative intracellular pathogen and potential biothreat agent. Evasion of the immune response contributes to the extraordinary virulence of this organism although the mechanism is unclear. Whereas wild-type strains induced low levels of cytokines, an F. tularensis ripA deletion mutant (LVSΔripA) provoked significant release of IL-1β, IL-18, and TNF-α by resting macrophages. IL-1β and IL-18 secretion was dependent on inflammasome components pyrin-caspase recruitment domain/apoptotic speck-containing protein with a caspase recruitment domain and caspase-1, and the TLR/IL-1R signaling molecule MyD88 was required for inflammatory cytokine synthesis. Complementation of LVSΔripA with a plasmid encoding ripA restored immune evasion. Similar findings were observed in a human monocytic line. The presence of ripA nearly eliminated activation of MAPKs including ERK1/2, JNK, and p38, and pharmacologic inhibitors of these three MAPKs reduced cytokine induction by LVSΔripA. Animals infected with LVSΔripA mounted a stronger IL-1β and TNF-α response than that of mice infected with wild-type live vaccine strain. This analysis revealed novel immune evasive mechanisms of F. tularensis. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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