Oral Challenge with Wild-Type Salmonella Typhi Induces Distinct Changes in B Cell Subsets in Individuals Who Develop Typhoid Disease.
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...
Saved in:
| Main Authors: | , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2016-06-01
|
| Series: | PLoS Neglected Tropical Diseases |
| Online Access: | https://journals.plos.org/plosntds/article/file?id=10.1371/journal.pntd.0004766&type=printable |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850138809206833152 |
|---|---|
| author | Franklin R Toapanta Paula J Bernal Stephanie Fresnay Laurence S Magder Thomas C Darton Claire Jones Claire S Waddington Christoph J Blohmke Brian Angus Myron M Levine Andrew J Pollard Marcelo B Sztein |
| author_facet | Franklin R Toapanta Paula J Bernal Stephanie Fresnay Laurence S Magder Thomas C Darton Claire Jones Claire S Waddington Christoph J Blohmke Brian Angus Myron M Levine Andrew J Pollard Marcelo B Sztein |
| author_sort | Franklin R Toapanta |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-6662c9eed7494cddb4ea33aa3199b8da |
| institution | OA Journals |
| issn | 1935-2727 1935-2735 |
| language | English |
| publishDate | 2016-06-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Neglected Tropical Diseases |
| spelling | doaj-art-6662c9eed7494cddb4ea33aa3199b8da2025-08-20T02:30:30ZengPublic Library of Science (PLoS)PLoS Neglected Tropical Diseases1935-27271935-27352016-06-01106e000476610.1371/journal.pntd.0004766Oral Challenge with Wild-Type Salmonella Typhi Induces Distinct Changes in B Cell Subsets in Individuals Who Develop Typhoid Disease.Franklin R ToapantaPaula J BernalStephanie FresnayLaurence S MagderThomas C DartonClaire JonesClaire S WaddingtonChristoph J BlohmkeBrian AngusMyron M LevineAndrew J PollardMarcelo B SzteinA 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.https://journals.plos.org/plosntds/article/file?id=10.1371/journal.pntd.0004766&type=printable |
| spellingShingle | Franklin R Toapanta Paula J Bernal Stephanie Fresnay Laurence S Magder Thomas C Darton Claire Jones Claire S Waddington Christoph J Blohmke Brian Angus Myron M Levine Andrew J Pollard Marcelo B Sztein Oral Challenge with Wild-Type Salmonella Typhi Induces Distinct Changes in B Cell Subsets in Individuals Who Develop Typhoid Disease. PLoS Neglected Tropical Diseases |
| title | Oral Challenge with Wild-Type Salmonella Typhi Induces Distinct Changes in B Cell Subsets in Individuals Who Develop Typhoid Disease. |
| title_full | Oral Challenge with Wild-Type Salmonella Typhi Induces Distinct Changes in B Cell Subsets in Individuals Who Develop Typhoid Disease. |
| title_fullStr | Oral Challenge with Wild-Type Salmonella Typhi Induces Distinct Changes in B Cell Subsets in Individuals Who Develop Typhoid Disease. |
| title_full_unstemmed | Oral Challenge with Wild-Type Salmonella Typhi Induces Distinct Changes in B Cell Subsets in Individuals Who Develop Typhoid Disease. |
| title_short | Oral Challenge with Wild-Type Salmonella Typhi Induces Distinct Changes in B Cell Subsets in Individuals Who Develop Typhoid Disease. |
| title_sort | oral challenge with wild type salmonella typhi induces distinct changes in b cell subsets in individuals who develop typhoid disease |
| url | https://journals.plos.org/plosntds/article/file?id=10.1371/journal.pntd.0004766&type=printable |
| work_keys_str_mv | AT franklinrtoapanta oralchallengewithwildtypesalmonellatyphiinducesdistinctchangesinbcellsubsetsinindividualswhodeveloptyphoiddisease AT paulajbernal oralchallengewithwildtypesalmonellatyphiinducesdistinctchangesinbcellsubsetsinindividualswhodeveloptyphoiddisease AT stephaniefresnay oralchallengewithwildtypesalmonellatyphiinducesdistinctchangesinbcellsubsetsinindividualswhodeveloptyphoiddisease AT laurencesmagder oralchallengewithwildtypesalmonellatyphiinducesdistinctchangesinbcellsubsetsinindividualswhodeveloptyphoiddisease AT thomascdarton oralchallengewithwildtypesalmonellatyphiinducesdistinctchangesinbcellsubsetsinindividualswhodeveloptyphoiddisease AT clairejones oralchallengewithwildtypesalmonellatyphiinducesdistinctchangesinbcellsubsetsinindividualswhodeveloptyphoiddisease AT claireswaddington oralchallengewithwildtypesalmonellatyphiinducesdistinctchangesinbcellsubsetsinindividualswhodeveloptyphoiddisease AT christophjblohmke oralchallengewithwildtypesalmonellatyphiinducesdistinctchangesinbcellsubsetsinindividualswhodeveloptyphoiddisease AT brianangus oralchallengewithwildtypesalmonellatyphiinducesdistinctchangesinbcellsubsetsinindividualswhodeveloptyphoiddisease AT myronmlevine oralchallengewithwildtypesalmonellatyphiinducesdistinctchangesinbcellsubsetsinindividualswhodeveloptyphoiddisease AT andrewjpollard oralchallengewithwildtypesalmonellatyphiinducesdistinctchangesinbcellsubsetsinindividualswhodeveloptyphoiddisease AT marcelobsztein oralchallengewithwildtypesalmonellatyphiinducesdistinctchangesinbcellsubsetsinindividualswhodeveloptyphoiddisease |