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Oral Challenge with Wild-Type Salmonella Typhi Induces Distinct Changes in B Cell Subsets in Individuals Who Develop Typhoid Disease
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نویسنده
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toapanta f.r. ,bernal p.j. ,fresnay s. ,magder l.s. ,darton t.c. ,jones c. ,waddington c.s. ,blohmke c.j. ,angus b. ,levine m.m. ,pollard a.j. ,sztein m.b.
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منبع
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plos neglected tropical diseases - 2016 - دوره : 10 - شماره : 6
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چکیده
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A novel human oral challenge model with wild-type salmonella typhi (s. typhi) was recently established by the oxford vaccine group. in this model,104 cfu of salmonella resulted in 65% of participants developing typhoid fever (referred here as typhoid diagnosis -td-) 6–9 days post-challenge. td was diagnosed in participants meeting clinical (oral temperature ≥38°c for ≥12h) and/or microbiological (s. typhi bacteremia) endpoints. changes in b cell subpopulations following s. typhi challenge remain undefined. to address this issue,a subset of volunteers (6 td and 4 who did not develop td -notd-) was evaluated. notable changes included reduction in the frequency of b cells (cells/ml) of td volunteers during disease days and increase in plasmablasts (pb) during the recovery phase (>day 14). additionally,a portion of pb of td volunteers showed a significant increase in activation (cd40,cd21) and gut homing (integrin α4β7) molecules. furthermore,all bm subsets of td volunteers showed changes induced by s. typhi infections such as a decrease in cd21 in switched memory (sm) cd27+ and sm cd27- cells as well as upregulation of cd40 in unswitched memory (um) and naïve cells. furthermore,changes in the signaling profile of some bm subsets were identified after s. typhi-lps stimulation around time of disease. notably,naïve cells of td (compared to notd) volunteers showed a higher percentage of cells phosphorylating akt suggesting enhanced survival of these cells. interestingly,most these changes were temporally associated with disease onset. this is the first study to describe differences in b cell subsets directly related to clinical outcome following oral challenge with wild-type s. typhi in humans. © 2016 toapanta et al.
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آدرس
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center for vaccine development,university of maryland school of medicine,baltimore,md,united states,department of medicine,university of maryland school of medicine,baltimore,md, United States, center for vaccine development,university of maryland school of medicine,baltimore,md,united states,department of pediatrics,university of maryland school of medicine,baltimore,md, United States, center for vaccine development,university of maryland school of medicine,baltimore,md,united states,department of pediatrics,university of maryland school of medicine,baltimore,md, United States, department of epidemiology and public health,university of maryland school of medicine,baltimore,md, United States, oxford vaccine group,department of paediatrics,university of oxford and the nihr oxford biomedical research centre,oxford, United Kingdom, oxford vaccine group,department of paediatrics,university of oxford and the nihr oxford biomedical research centre,oxford, United Kingdom, oxford vaccine group,department of paediatrics,university of oxford and the nihr oxford biomedical research centre,oxford, United Kingdom, oxford vaccine group,department of paediatrics,university of oxford and the nihr oxford biomedical research centre,oxford, United Kingdom, nuffield department of medicine,university of oxford,oxford, United Kingdom, center for vaccine development,university of maryland school of medicine,baltimore,md,united states,department of medicine,university of maryland school of medicine,baltimore,md,united states,department of pediatrics,university of maryland school of medicine,baltimore,md, United States, oxford vaccine group,department of paediatrics,university of oxford and the nihr oxford biomedical research centre,oxford, United Kingdom, center for vaccine development,university of maryland school of medicine,baltimore,md,united states,department of medicine,university of maryland school of medicine,baltimore,md,united states,department of pediatrics,university of maryland school of medicine,baltimore,md, United States
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Authors
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