Oral Challenge with Wild-Type Salmonella Typhi Induces Distinct Changes in B Cell Subsets in Individuals Who Develop Typhoid Disease
Publication Date
June 14, 2016
Journal
PLOS Neglected Tropical Diseases
Authors
Franklin R. Toapanta, Paula J. Bernal, Stephanie Fresnay, Laurence S. Magder, et al
Volume
10
Issue
6
Pages
e0004766
DOI
https://dx.plos.org/10.1371/journal.pntd.0004766
Publisher URL
http://journals.plos.org/plosntds/article?id=10.1371%2Fjournal.pntd.0004766
Scopus
84978047756
Mendeley
http://www.mendeley.com/research/oral-challenge-wildtype-salmonella-typhi-induces-distinct-changes-b-cell-subsets-individuals-develop
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Mendeley | Further Information

{"title"=>"Oral Challenge with Wild-Type Salmonella Typhi Induces Distinct Changes in B Cell Subsets in Individuals Who Develop Typhoid Disease", "type"=>"journal", "authors"=>[{"first_name"=>"Franklin R.", "last_name"=>"Toapanta", "scopus_author_id"=>"6506172880"}, {"first_name"=>"Paula J.", "last_name"=>"Bernal", "scopus_author_id"=>"55979683900"}, {"first_name"=>"Stephanie", "last_name"=>"Fresnay", "scopus_author_id"=>"6506081476"}, {"first_name"=>"Laurence S.", "last_name"=>"Magder", "scopus_author_id"=>"7003627816"}, {"first_name"=>"Thomas C.", "last_name"=>"Darton", "scopus_author_id"=>"26027413200"}, {"first_name"=>"Claire", "last_name"=>"Jones", "scopus_author_id"=>"57198787491"}, {"first_name"=>"Claire S.", "last_name"=>"Waddington", "scopus_author_id"=>"36132561400"}, {"first_name"=>"Christoph J.", "last_name"=>"Blohmke", "scopus_author_id"=>"24467220700"}, {"first_name"=>"Brian", "last_name"=>"Angus", "scopus_author_id"=>"56496580800"}, {"first_name"=>"Myron M.", "last_name"=>"Levine", "scopus_author_id"=>"35394847200"}, {"first_name"=>"Andrew J.", "last_name"=>"Pollard", "scopus_author_id"=>"7103193821"}, {"first_name"=>"Marcelo B.", "last_name"=>"Sztein", "scopus_author_id"=>"7005394979"}], "year"=>2016, "source"=>"PLoS Neglected Tropical Diseases", "identifiers"=>{"pmid"=>"27300136", "sgr"=>"84978047756", "doi"=>"10.1371/journal.pntd.0004766", "scopus"=>"2-s2.0-84978047756", "pui"=>"611099189", "isbn"=>"1935-2727", "issn"=>"19352735"}, "id"=>"ac154ca5-dc26-3e42-95ad-c672a6b3823c", "abstract"=>"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 degrees 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 alpha4beta7) 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 Naive cells. Furthermore, changes in the signaling profile of some BM subsets were identified after S. Typhi-LPS stimulation around time of disease. Notably, naive 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.", "link"=>"http://www.mendeley.com/research/oral-challenge-wildtype-salmonella-typhi-induces-distinct-changes-b-cell-subsets-individuals-develop", "reader_count"=>15, "reader_count_by_academic_status"=>{"Unspecified"=>1, "Researcher"=>5, "Student > Doctoral Student"=>1, "Student > Ph. D. Student"=>2, "Student > Postgraduate"=>2, "Student > Master"=>1, "Other"=>1, "Student > Bachelor"=>2}, "reader_count_by_user_role"=>{"Unspecified"=>1, "Researcher"=>5, "Student > Doctoral Student"=>1, "Student > Ph. D. Student"=>2, "Student > Postgraduate"=>2, "Student > Master"=>1, "Other"=>1, "Student > Bachelor"=>2}, "reader_count_by_subject_area"=>{"Unspecified"=>1, "Biochemistry, Genetics and Molecular Biology"=>1, "Agricultural and Biological Sciences"=>3, "Medicine and Dentistry"=>4, "Veterinary Science and Veterinary Medicine"=>1, "Immunology and Microbiology"=>5}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>4}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>5}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>3}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>1}, "Unspecified"=>{"Unspecified"=>1}, "Veterinary Science and Veterinary Medicine"=>{"Veterinary Science and Veterinary Medicine"=>1}}, "group_count"=>1}

Scopus | Further Information

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