Targeting Xcr1 on Dendritic Cells Rapidly Induce Th1-Associated Immune Responses That Contribute to Protection Against Influenza Infection
Targeting antigen to conventional dendritic cells (cDCs) can improve antigen-specific immune responses and additionally be used to influence the polarization of the immune responses. However, the mechanisms by which this is achieved are less clear. To improve our understanding, we here evaluate mole...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-02-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2022.752714/full |
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| author | Demo Yemane Tesfaye Demo Yemane Tesfaye Sonja Bobic Sonja Bobic Anna Lysén Anna Lysén Peter Csaba Huszthy Peter Csaba Huszthy Arnar Gudjonsson Arnar Gudjonsson Ranveig Braathen Ranveig Braathen Bjarne Bogen Bjarne Bogen Bjarne Bogen Even Fossum Even Fossum |
| author_facet | Demo Yemane Tesfaye Demo Yemane Tesfaye Sonja Bobic Sonja Bobic Anna Lysén Anna Lysén Peter Csaba Huszthy Peter Csaba Huszthy Arnar Gudjonsson Arnar Gudjonsson Ranveig Braathen Ranveig Braathen Bjarne Bogen Bjarne Bogen Bjarne Bogen Even Fossum Even Fossum |
| author_sort | Demo Yemane Tesfaye |
| collection | DOAJ |
| description | Targeting antigen to conventional dendritic cells (cDCs) can improve antigen-specific immune responses and additionally be used to influence the polarization of the immune responses. However, the mechanisms by which this is achieved are less clear. To improve our understanding, we here evaluate molecular and cellular requirements for CD4+ T cell and antibody polarization after immunization with Xcl1-fusion vaccines that specifically target cDC1s. Xcl1-fusion vaccines induced an IgG2a/IgG2b-dominated antibody response and rapid polarization of Th1 cells both in vitro and in vivo. For comparison, we included fliC-fusion vaccines that almost exclusively induced IgG1, despite inducing a more mixed polarization of T cells. Th1 polarization and IgG2a induction with Xcl1-fusion vaccines required IL-12 secretion but were nevertheless maintained in BATF3-/- mice which lack IL-12-secreting migratory DCs. Interestingly, induction of IgG2a-dominated responses was highly dependent on the early kinetics of Th1 induction and was important for optimal protection in an influenza infection model. Early Th1 induction was dominant, since a combined Xcl1- and fliC-fusion vaccine induced IgG2a/IgG2b polarized antibody responses similar to Xcl1-fusion vaccines alone. In summary, our results demonstrate that targeting antigen to Xcr1+ cDC1s is an efficient strategy for enhancing IgG2a antibody responses through rapid Th1 induction, which can be utilized for improved vaccine design. |
| first_indexed | 2024-12-20T19:14:14Z |
| format | Article |
| id | doaj.art-5453121082fc42ef863447fc1290adc0 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-20T19:14:14Z |
| publishDate | 2022-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-5453121082fc42ef863447fc1290adc02022-12-21T19:29:08ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-02-011310.3389/fimmu.2022.752714752714Targeting Xcr1 on Dendritic Cells Rapidly Induce Th1-Associated Immune Responses That Contribute to Protection Against Influenza InfectionDemo Yemane Tesfaye0Demo Yemane Tesfaye1Sonja Bobic2Sonja Bobic3Anna Lysén4Anna Lysén5Peter Csaba Huszthy6Peter Csaba Huszthy7Arnar Gudjonsson8Arnar Gudjonsson9Ranveig Braathen10Ranveig Braathen11Bjarne Bogen12Bjarne Bogen13Bjarne Bogen14Even Fossum15Even Fossum16Department of Immunology, Division of Laboratory Medicine, Oslo University Hospital, Oslo, NorwayKristian Gerhard Jebsen Center for Research on Influenza Vaccines, University of Oslo and Oslo University Hospital, Oslo, NorwayDepartment of Immunology, Division of Laboratory Medicine, Oslo University Hospital, Oslo, NorwayKristian Gerhard Jebsen Center for Research on Influenza Vaccines, University of Oslo and Oslo University Hospital, Oslo, NorwayDepartment of Immunology, Division of Laboratory Medicine, Oslo University Hospital, Oslo, NorwayKristian Gerhard Jebsen Center for Research on Influenza Vaccines, University of Oslo and Oslo University Hospital, Oslo, NorwayDepartment of Immunology, Division of Laboratory Medicine, Oslo University Hospital, Oslo, NorwayCenter for Immune Regulation, Institute of Immunology, University of Oslo and Oslo University Hospital Rikshospitalet, Oslo, NorwayDepartment of Immunology, Division of Laboratory Medicine, Oslo University Hospital, Oslo, NorwayKristian Gerhard Jebsen Center for Research on Influenza Vaccines, University of Oslo and Oslo University Hospital, Oslo, NorwayDepartment of Immunology, Division of Laboratory Medicine, Oslo University Hospital, Oslo, NorwayKristian Gerhard Jebsen Center for Research on Influenza Vaccines, University of Oslo and Oslo University Hospital, Oslo, NorwayDepartment of Immunology, Division of Laboratory Medicine, Oslo University Hospital, Oslo, NorwayKristian Gerhard Jebsen Center for Research on Influenza Vaccines, University of Oslo and Oslo University Hospital, Oslo, NorwayCenter for Immune Regulation, Institute of Immunology, University of Oslo and Oslo University Hospital Rikshospitalet, Oslo, NorwayDepartment of Immunology, Division of Laboratory Medicine, Oslo University Hospital, Oslo, NorwayKristian Gerhard Jebsen Center for Research on Influenza Vaccines, University of Oslo and Oslo University Hospital, Oslo, NorwayTargeting antigen to conventional dendritic cells (cDCs) can improve antigen-specific immune responses and additionally be used to influence the polarization of the immune responses. However, the mechanisms by which this is achieved are less clear. To improve our understanding, we here evaluate molecular and cellular requirements for CD4+ T cell and antibody polarization after immunization with Xcl1-fusion vaccines that specifically target cDC1s. Xcl1-fusion vaccines induced an IgG2a/IgG2b-dominated antibody response and rapid polarization of Th1 cells both in vitro and in vivo. For comparison, we included fliC-fusion vaccines that almost exclusively induced IgG1, despite inducing a more mixed polarization of T cells. Th1 polarization and IgG2a induction with Xcl1-fusion vaccines required IL-12 secretion but were nevertheless maintained in BATF3-/- mice which lack IL-12-secreting migratory DCs. Interestingly, induction of IgG2a-dominated responses was highly dependent on the early kinetics of Th1 induction and was important for optimal protection in an influenza infection model. Early Th1 induction was dominant, since a combined Xcl1- and fliC-fusion vaccine induced IgG2a/IgG2b polarized antibody responses similar to Xcl1-fusion vaccines alone. In summary, our results demonstrate that targeting antigen to Xcr1+ cDC1s is an efficient strategy for enhancing IgG2a antibody responses through rapid Th1 induction, which can be utilized for improved vaccine design.https://www.frontiersin.org/articles/10.3389/fimmu.2022.752714/fulldendritic cellsXCR1Th1IgG2atargeting |
| spellingShingle | Demo Yemane Tesfaye Demo Yemane Tesfaye Sonja Bobic Sonja Bobic Anna Lysén Anna Lysén Peter Csaba Huszthy Peter Csaba Huszthy Arnar Gudjonsson Arnar Gudjonsson Ranveig Braathen Ranveig Braathen Bjarne Bogen Bjarne Bogen Bjarne Bogen Even Fossum Even Fossum Targeting Xcr1 on Dendritic Cells Rapidly Induce Th1-Associated Immune Responses That Contribute to Protection Against Influenza Infection Frontiers in Immunology dendritic cells XCR1 Th1 IgG2a targeting |
| title | Targeting Xcr1 on Dendritic Cells Rapidly Induce Th1-Associated Immune Responses That Contribute to Protection Against Influenza Infection |
| title_full | Targeting Xcr1 on Dendritic Cells Rapidly Induce Th1-Associated Immune Responses That Contribute to Protection Against Influenza Infection |
| title_fullStr | Targeting Xcr1 on Dendritic Cells Rapidly Induce Th1-Associated Immune Responses That Contribute to Protection Against Influenza Infection |
| title_full_unstemmed | Targeting Xcr1 on Dendritic Cells Rapidly Induce Th1-Associated Immune Responses That Contribute to Protection Against Influenza Infection |
| title_short | Targeting Xcr1 on Dendritic Cells Rapidly Induce Th1-Associated Immune Responses That Contribute to Protection Against Influenza Infection |
| title_sort | targeting xcr1 on dendritic cells rapidly induce th1 associated immune responses that contribute to protection against influenza infection |
| topic | dendritic cells XCR1 Th1 IgG2a targeting |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2022.752714/full |
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