Distinct early cellular kinetics in participants protected against colonization upon Bordetella pertussis challenge
Distinct early cellular kinetics in participants protected against colonization upon Bordetella pertussis challenge
BACKGROUND. To date, only limited data are available on the mechanisms of protection against colonization with Bordetella pertussis in humans.
METHODS. In this study, the cellular responses to B. pertussis challenge were monitored longitudinally using high-dimensional EuroFlow-based flow cytometry, allowing quantitative detection of more than 250 different immune cell subsets in the blood of 15 healthy donors.
RESULTS. Participants who were protected against colonization showed different early cellular responses compared with colonized participants. Especially prominent for colonization-protected participants were the early expansion of CD36– nonclassical monocytes on day 1 (D1), natural killer cells (D3), follicular T helper cells (D1–D3), and plasma cells (D3). Plasma cell expansion on D3 correlated negatively with the CFU load on D7 and D9 after challenge. Increased plasma cell maturation on D11–D14 was found in participants with seroconversion.
CONCLUSION. These early cellular immune responses following experimental infection can now be further characterized and potentially linked to an efficient mucosal immune response, preventing colonization. Ultimately, their presence may be used to evaluate whether new B. pertussis vaccine candidates are protective against B. pertussis colonization, e.g., by bacterial challenge after vaccination.
TRIAL REGISTRATION. ClinicalTrials.gov NCT03751514.
FUNDING. Innovative Medicines Initiative 2 Joint Undertaking and the EuroFlow Consortium.
Diks, Annieck m.
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De graaf, Hans
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Teodosio, Cristina
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Groenland, Rick j.
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De mooij, Bas
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Ibrahim, Muktar
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Hill, Alison r.
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Read, Robert c.
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Van dongen, Jacques j.m.
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Berkowska, Magdalena a.
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1 March 2023
Diks, Annieck m.
f43f045b-7618-4579-b1fe-bf06d1e91985
De graaf, Hans
447e78ed-346f-45bb-9238-fce2118d5559
Teodosio, Cristina
9d367222-6e90-4cc3-b466-f8b62523d4ec
Groenland, Rick j.
64d16359-a79a-48fd-ace8-bbc9b5197dfd
De mooij, Bas
fbf3a96f-9393-4c06-9e48-31503caceeed
Ibrahim, Muktar
15bab4d1-f800-4d51-9ac6-d7999bd2a5d2
Hill, Alison r.
55020310-08eb-4a32-97fb-94c7bed2ec38
Read, Robert c.
b5caca7b-0063-438a-b703-7ecbb6fc2b51
Van dongen, Jacques j.m.
1ea63baf-9951-4b06-991c-0132283b29bd
Berkowska, Magdalena a.
4ae275ab-b4d2-44bb-8cf8-98ab78747039
Diks, Annieck m., De graaf, Hans, Teodosio, Cristina, Groenland, Rick j., De mooij, Bas, Ibrahim, Muktar, Hill, Alison r., Read, Robert c., Van dongen, Jacques j.m. and Berkowska, Magdalena a.
(2023)
Distinct early cellular kinetics in participants protected against colonization upon Bordetella pertussis challenge.
Journal of Clinical Investigation, 133 (5), [e163121].
(doi:10.1172/JCI163121).
Abstract
BACKGROUND. To date, only limited data are available on the mechanisms of protection against colonization with Bordetella pertussis in humans.
METHODS. In this study, the cellular responses to B. pertussis challenge were monitored longitudinally using high-dimensional EuroFlow-based flow cytometry, allowing quantitative detection of more than 250 different immune cell subsets in the blood of 15 healthy donors.
RESULTS. Participants who were protected against colonization showed different early cellular responses compared with colonized participants. Especially prominent for colonization-protected participants were the early expansion of CD36– nonclassical monocytes on day 1 (D1), natural killer cells (D3), follicular T helper cells (D1–D3), and plasma cells (D3). Plasma cell expansion on D3 correlated negatively with the CFU load on D7 and D9 after challenge. Increased plasma cell maturation on D11–D14 was found in participants with seroconversion.
CONCLUSION. These early cellular immune responses following experimental infection can now be further characterized and potentially linked to an efficient mucosal immune response, preventing colonization. Ultimately, their presence may be used to evaluate whether new B. pertussis vaccine candidates are protective against B. pertussis colonization, e.g., by bacterial challenge after vaccination.
TRIAL REGISTRATION. ClinicalTrials.gov NCT03751514.
FUNDING. Innovative Medicines Initiative 2 Joint Undertaking and the EuroFlow Consortium.
Text
163121.2-20230227143140-covered-e0fd13ba177f913fd3156f593ead4cfd
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Accepted/In Press date: 10 January 2023
e-pub ahead of print date: 17 January 2023
Published date: 1 March 2023
Identifiers
Local EPrints ID: 491207
URI: http://eprints.soton.ac.uk/id/eprint/491207
ISSN: 0021-9738
PURE UUID: 2c07ae27-0418-4ae2-8458-1ca46b1205c2
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Date deposited: 17 Jun 2024 16:48
Last modified: 22 Jun 2024 01:45
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Contributors
Author:
Annieck m. Diks
Author:
Hans De graaf
Author:
Cristina Teodosio
Author:
Rick j. Groenland
Author:
Bas De mooij
Author:
Muktar Ibrahim
Author:
Alison r. Hill
Author:
Jacques j.m. Van dongen
Author:
Magdalena a. Berkowska
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