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, all...
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
American Society for Clinical Investigation
2023-03-01
|
| Series: | The Journal of Clinical Investigation |
| Subjects: | |
| Online Access: | https://doi.org/10.1172/JCI163121 |
| _version_ | 1827768180221673472 |
|---|---|
| author | Annieck M. Diks Hans de Graaf Cristina Teodosio Rick J. Groenland Bas de Mooij Muktar Ibrahim Alison R. Hill Robert C. Read Jacques J.M. van Dongen Magdalena A. Berkowska on behalf of the IMI-2 PERISCOPE Consortium |
| author_facet | Annieck M. Diks Hans de Graaf Cristina Teodosio Rick J. Groenland Bas de Mooij Muktar Ibrahim Alison R. Hill Robert C. Read Jacques J.M. van Dongen Magdalena A. Berkowska on behalf of the IMI-2 PERISCOPE Consortium |
| author_sort | Annieck M. Diks |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-11T12:08:45Z |
| format | Article |
| id | doaj.art-580ba9981ff247b7ae674ff31d83cabc |
| institution | Directory Open Access Journal |
| issn | 1558-8238 |
| language | English |
| last_indexed | 2024-03-11T12:08:45Z |
| publishDate | 2023-03-01 |
| publisher | American Society for Clinical Investigation |
| record_format | Article |
| series | The Journal of Clinical Investigation |
| spelling | doaj.art-580ba9981ff247b7ae674ff31d83cabc2023-11-07T16:20:00ZengAmerican Society for Clinical InvestigationThe Journal of Clinical Investigation1558-82382023-03-011335Distinct early cellular kinetics in participants protected against colonization upon Bordetella pertussis challengeAnnieck M. DiksHans de GraafCristina TeodosioRick J. GroenlandBas de MooijMuktar IbrahimAlison R. HillRobert C. ReadJacques J.M. van DongenMagdalena A. Berkowskaon behalf of the IMI-2 PERISCOPE ConsortiumBACKGROUND 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.https://doi.org/10.1172/JCI163121ImmunologyInfectious disease |
| spellingShingle | Annieck M. Diks Hans de Graaf Cristina Teodosio Rick J. Groenland Bas de Mooij Muktar Ibrahim Alison R. Hill Robert C. Read Jacques J.M. van Dongen Magdalena A. Berkowska on behalf of the IMI-2 PERISCOPE Consortium Distinct early cellular kinetics in participants protected against colonization upon Bordetella pertussis challenge The Journal of Clinical Investigation Immunology Infectious disease |
| title | Distinct early cellular kinetics in participants protected against colonization upon Bordetella pertussis challenge |
| title_full | Distinct early cellular kinetics in participants protected against colonization upon Bordetella pertussis challenge |
| title_fullStr | Distinct early cellular kinetics in participants protected against colonization upon Bordetella pertussis challenge |
| title_full_unstemmed | Distinct early cellular kinetics in participants protected against colonization upon Bordetella pertussis challenge |
| title_short | Distinct early cellular kinetics in participants protected against colonization upon Bordetella pertussis challenge |
| title_sort | distinct early cellular kinetics in participants protected against colonization upon bordetella pertussis challenge |
| topic | Immunology Infectious disease |
| url | https://doi.org/10.1172/JCI163121 |
| work_keys_str_mv | AT annieckmdiks distinctearlycellularkineticsinparticipantsprotectedagainstcolonizationuponbordetellapertussischallenge AT hansdegraaf distinctearlycellularkineticsinparticipantsprotectedagainstcolonizationuponbordetellapertussischallenge AT cristinateodosio distinctearlycellularkineticsinparticipantsprotectedagainstcolonizationuponbordetellapertussischallenge AT rickjgroenland distinctearlycellularkineticsinparticipantsprotectedagainstcolonizationuponbordetellapertussischallenge AT basdemooij distinctearlycellularkineticsinparticipantsprotectedagainstcolonizationuponbordetellapertussischallenge AT muktaribrahim distinctearlycellularkineticsinparticipantsprotectedagainstcolonizationuponbordetellapertussischallenge AT alisonrhill distinctearlycellularkineticsinparticipantsprotectedagainstcolonizationuponbordetellapertussischallenge AT robertcread distinctearlycellularkineticsinparticipantsprotectedagainstcolonizationuponbordetellapertussischallenge AT jacquesjmvandongen distinctearlycellularkineticsinparticipantsprotectedagainstcolonizationuponbordetellapertussischallenge AT magdalenaaberkowska distinctearlycellularkineticsinparticipantsprotectedagainstcolonizationuponbordetellapertussischallenge AT onbehalfoftheimi2periscopeconsortium distinctearlycellularkineticsinparticipantsprotectedagainstcolonizationuponbordetellapertussischallenge |