Staphylococcus aureus alpha toxin suppresses effective innate and adaptive immune responses in a murine dermonecrosis model.
Staphylococcus aureus alpha toxin suppresses effective innate and adaptive immune responses in a murine dermonecrosis model.
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DOI：
10.1371/journal.pone.0075103
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Sellman BR
中科院分区：
文献类型：
--
作者：
Tkaczyk C;Hamilton MM;Datta V;Yang XP;Hilliard JJ;Stephens GL;Sadowska A;Hua L;O'Day T;Suzich J;Stover CK;Sellman BR
An optimal host response against Staphylococcus aureus skin and soft tissue infections (SSTI) is dependent on IL-1β and IL-17 mediated abscess formation. Alpha toxin (AT), an essential virulence factor for SSTI, has been reported to damage tissue integrity; however its effect on the immune response has not been investigated. Here, we demonstrate that infection with USA300 AT isogenic mutant (Δhla), or passive immunization with an AT neutralizing mAb, 2A3, 24 h prior to infection with wild type USA300 (WT), resulted in dermonecrotic lesion size reduction, and robust neutrophil infiltration. Infiltration correlates with increase in proinflammatory cytokines and chemokines, as well as enhanced bacterial clearance relative to immunization with a negative control mAb. In addition, infection with Δhla, or with WT +2A3, resulted in an early influx of innate IL-17+γδT cells and a more rapid induction of an adaptive immune response as measured by Th1 and Th17 cell recruitment at the site of infection. These results are the first direct evidence of a role for AT in subverting the innate and adaptive immune responses during a S. aureus SSTI. Further, these effects of AT can be overcome with a high affinity anti-AT mAb resulting in a reduction in disease severity.
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影响因子：
168.9
作者：
DeLeo, Frank R.;Otto, Michael;Kreiswirth, Barry N.;Chambers, Henry F.
通讯作者：
Chambers, Henry F.
DOI：
10.1038/nri2782
发表时间：
2010-06
期刊：
Nature reviews. Immunology
影响因子：
--
作者：
通讯作者：
--
影响因子：
6.4
作者：
Kobayashi, Scott D.;Malachowa, Natalia;DeLeo, Frank R.
通讯作者：
DeLeo, Frank R.
DOI：
10.1073/pnas.0904958106
发表时间：
2009-08-04
影响因子：
11.1
作者：
Hruz, Petr;Zinkernagel, Annelies S.;Eckmann, Lars
通讯作者：
Eckmann, Lars
影响因子：
6.7
作者：
Lin L;Ibrahim AS;Xu X;Farber JM;Avanesian V;Baquir B;Fu Y;French SW;Edwards JE Jr;Spellberg B
通讯作者：
Spellberg B