Th1/Th17 T cell Tissue-Resident Immunity Increases Protection, But Is Not Required in a Vaccine Strategy Against Genital Infection With Chlamydia trachomatis

The requirement for vaccine-induced tissue-resident immunity for protection against one or repeated infections with Chlamydia trachomatis (C.t.) is still not fully resolved. In this study, our aim was to investigate to which degree tissue-resident Th1/Th17 T cells in the genital tract (GT) could add...

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Autores principales: Nina Dieu Nhien Tran Nguyen, Safia Guleed, Anja Weinreich Olsen, Frank Follmann, Jan Pravsgaard Christensen, Jes Dietrich
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Publicado: Frontiers Media S.A. 2021
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spelling oai:doaj.org-article:078292d308f347e59800f891f7af49242021-12-02T06:14:24ZTh1/Th17 T cell Tissue-Resident Immunity Increases Protection, But Is Not Required in a Vaccine Strategy Against Genital Infection With Chlamydia trachomatis1664-322410.3389/fimmu.2021.790463https://doaj.org/article/078292d308f347e59800f891f7af49242021-12-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fimmu.2021.790463/fullhttps://doaj.org/toc/1664-3224The requirement for vaccine-induced tissue-resident immunity for protection against one or repeated infections with Chlamydia trachomatis (C.t.) is still not fully resolved. In this study, our aim was to investigate to which degree tissue-resident Th1/Th17 T cells in the genital tract (GT) could add to the protection mediated by circulating immunity. Out of several mucosal vaccine strategies, a strategy termed SIM (for simultaneous intrauterine and parenteral immunization with CAF01 adjuvanted CTH522), was superior in generating genital tract tissue-resident Th1/Th17 T cell immunity. This led to a faster and stronger local CD4 T cell response post infection, consisting of multifunctional IFNγ/TNFα-producing Th1 T cells and IFNγ/TNFα/IL-17-producing Th17 T cells, and a faster recruitment of innate immune cells. Post infection, SIM animals showed an additional significant reduction in bacterial levels compared to mice having received only a parenteral vaccine. Nevertheless, the parenteral strategy reduced bacterial levels by 75%, and interestingly, post infection, these mice generated their own vaccine-derived genital tract tissue-resident memory Th1/Th17 T cells, which upon a subsequent infection showed as fast an activation in the genital tract, as observed in SIM mice. Furthermore, in contrast to after the first infection, both groups of mice now showed a similar infection-induced boost in local vaginal IgA and IgG titers. Thus, vaccine-induced resident immunity, generated pre-infection, led to an advantage in the response against the first infection, but not the second infection, suggesting that a parenteral vaccine strategy is a suitable vaccine strategy against infections with Chlamydia trachomatis.Nina Dieu Nhien Tran NguyenSafia GuleedAnja Weinreich OlsenFrank FollmannJan Pravsgaard ChristensenJes DietrichFrontiers Media S.A.articlevaccineTh1Th17infectionChlamydiaImmunologic diseases. AllergyRC581-607ENFrontiers in Immunology, Vol 12 (2021)
institution DOAJ
collection DOAJ
language EN
topic vaccine
Th1
Th17
infection
Chlamydia
Immunologic diseases. Allergy
RC581-607
spellingShingle vaccine
Th1
Th17
infection
Chlamydia
Immunologic diseases. Allergy
RC581-607
Nina Dieu Nhien Tran Nguyen
Safia Guleed
Anja Weinreich Olsen
Frank Follmann
Jan Pravsgaard Christensen
Jes Dietrich
Th1/Th17 T cell Tissue-Resident Immunity Increases Protection, But Is Not Required in a Vaccine Strategy Against Genital Infection With Chlamydia trachomatis
description The requirement for vaccine-induced tissue-resident immunity for protection against one or repeated infections with Chlamydia trachomatis (C.t.) is still not fully resolved. In this study, our aim was to investigate to which degree tissue-resident Th1/Th17 T cells in the genital tract (GT) could add to the protection mediated by circulating immunity. Out of several mucosal vaccine strategies, a strategy termed SIM (for simultaneous intrauterine and parenteral immunization with CAF01 adjuvanted CTH522), was superior in generating genital tract tissue-resident Th1/Th17 T cell immunity. This led to a faster and stronger local CD4 T cell response post infection, consisting of multifunctional IFNγ/TNFα-producing Th1 T cells and IFNγ/TNFα/IL-17-producing Th17 T cells, and a faster recruitment of innate immune cells. Post infection, SIM animals showed an additional significant reduction in bacterial levels compared to mice having received only a parenteral vaccine. Nevertheless, the parenteral strategy reduced bacterial levels by 75%, and interestingly, post infection, these mice generated their own vaccine-derived genital tract tissue-resident memory Th1/Th17 T cells, which upon a subsequent infection showed as fast an activation in the genital tract, as observed in SIM mice. Furthermore, in contrast to after the first infection, both groups of mice now showed a similar infection-induced boost in local vaginal IgA and IgG titers. Thus, vaccine-induced resident immunity, generated pre-infection, led to an advantage in the response against the first infection, but not the second infection, suggesting that a parenteral vaccine strategy is a suitable vaccine strategy against infections with Chlamydia trachomatis.
format article
author Nina Dieu Nhien Tran Nguyen
Safia Guleed
Anja Weinreich Olsen
Frank Follmann
Jan Pravsgaard Christensen
Jes Dietrich
author_facet Nina Dieu Nhien Tran Nguyen
Safia Guleed
Anja Weinreich Olsen
Frank Follmann
Jan Pravsgaard Christensen
Jes Dietrich
author_sort Nina Dieu Nhien Tran Nguyen
title Th1/Th17 T cell Tissue-Resident Immunity Increases Protection, But Is Not Required in a Vaccine Strategy Against Genital Infection With Chlamydia trachomatis
title_short Th1/Th17 T cell Tissue-Resident Immunity Increases Protection, But Is Not Required in a Vaccine Strategy Against Genital Infection With Chlamydia trachomatis
title_full Th1/Th17 T cell Tissue-Resident Immunity Increases Protection, But Is Not Required in a Vaccine Strategy Against Genital Infection With Chlamydia trachomatis
title_fullStr Th1/Th17 T cell Tissue-Resident Immunity Increases Protection, But Is Not Required in a Vaccine Strategy Against Genital Infection With Chlamydia trachomatis
title_full_unstemmed Th1/Th17 T cell Tissue-Resident Immunity Increases Protection, But Is Not Required in a Vaccine Strategy Against Genital Infection With Chlamydia trachomatis
title_sort th1/th17 t cell tissue-resident immunity increases protection, but is not required in a vaccine strategy against genital infection with chlamydia trachomatis
publisher Frontiers Media S.A.
publishDate 2021
url https://doaj.org/article/078292d308f347e59800f891f7af4924
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