IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v15y2024i1d10.1038_s41467-024-54644-w.html
   My bibliography  Save this article

Pathobiont-induced suppressive immune imprints thwart T cell vaccine responses

Author

Listed:
  • Irshad Ahmed Hajam

    (University of California San Diego)

  • Chih-Ming Tsai

    (University of California San Diego)

  • Cesia Gonzalez

    (University of California San Diego)

  • Juan Raphael Caldera

    (University of California San Diego
    33608 Ortega Hwy.)

  • María Lázaro Díez

    (University of California San Diego
    Badalona)

  • Xin Du

    (University of California San Diego)

  • April Aralar

    (University of California San Diego)

  • Brian Lin

    (University of California San Diego)

  • William Duong

    (University of California San Diego)

  • George Y. Liu

    (University of California San Diego
    Rady Children’s Hospital)

Abstract

Pathobionts have evolved many strategies to coexist with the host, but how immune evasion mechanisms contribute to the difficulty of developing vaccines against pathobionts is unclear. Meanwhile, Staphylococcus aureus (SA) has resisted human vaccine development to date. Here we show that prior SA exposure induces non-protective CD4+ T cell imprints, leading to the blunting of protective IsdB vaccine responses. Mechanistically, these SA-experienced CD4+ T cells express IL-10, which is further amplified by vaccination and impedes vaccine protection by binding with IL-10Rα on CD4+ T cell and inhibit IL-17A production. IL-10 also mediates cross-suppression of IsdB and sdrE multi-antigen vaccine. By contrast, the inefficiency of SA IsdB, IsdA and MntC vaccines can be overcome by co-treatment with adjuvants that promote IL-17A and IFN-γ responses. We thus propose that IL-10 secreting, SA-experienced CD4+ T cell imprints represent a staphylococcal immune escaping mechanism that needs to be taken into consideration for future vaccine development.

Suggested Citation

  • Irshad Ahmed Hajam & Chih-Ming Tsai & Cesia Gonzalez & Juan Raphael Caldera & María Lázaro Díez & Xin Du & April Aralar & Brian Lin & William Duong & George Y. Liu, 2024. "Pathobiont-induced suppressive immune imprints thwart T cell vaccine responses," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
  • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-54644-w
    DOI: 10.1038/s41467-024-54644-w
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-024-54644-w
    File Function: Abstract
    Download Restriction: no

    File URL: https://libkey.io/10.1038/s41467-024-54644-w?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. Xiaokai Zhang & Tingrong Xiong & Lin Gao & Yu Wang & Luxuan Liu & Tian Tian & Yun Shi & Jinyong Zhang & Zhuo Zhao & Dongshui Lu & Ping Luo & Weijun Zhang & Ping Cheng & Haiming Jing & Qiang Gou & Hao , 2022. "Extracellular fibrinogen-binding protein released by intracellular Staphylococcus aureus suppresses host immunity by targeting TRAF3," Nature Communications, Nature, vol. 13(1), pages 1-11, December.
    2. Yasmine Belkaid & Ciriaco A. Piccirillo & Susana Mendez & Ethan M. Shevach & David L. Sacks, 2002. "CD4+CD25+ regulatory T cells control Leishmania major persistence and immunity," Nature, Nature, vol. 420(6915), pages 502-507, December.
    3. Koji Atarashi & Junichi Nishimura & Tatsuichiro Shima & Yoshinori Umesaki & Masahiro Yamamoto & Masaharu Onoue & Hideo Yagita & Naoto Ishii & Richard Evans & Kenya Honda & Kiyoshi Takeda, 2008. "ATP drives lamina propria TH17 cell differentiation," Nature, Nature, vol. 455(7214), pages 808-812, October.
    4. David Gerlach & Yinglan Guo & Cristina De Castro & Sun-Hwa Kim & Katja Schlatterer & Fei-Fei Xu & Claney Pereira & Peter H. Seeberger & Sara Ali & Jeroen Codée & Wanchat Sirisarn & Berit Schulte & Chr, 2018. "Methicillin-resistant Staphylococcus aureus alters cell wall glycosylation to evade immunity," Nature, Nature, vol. 563(7733), pages 705-709, November.
    Full references (including those not matched with items on IDEAS)

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Adélaïde Gélineau & Geneviève Marcelin & Melissa Ouhachi & Sébastien Dussaud & Lise Voland & Raoul Manuel & Ines Baba & Christine Rouault & Laurent Yvan-Charvet & Karine Clément & Roxane Tussiwand & T, 2024. "Fructooligosaccharides benefits on glucose homeostasis upon high-fat diet feeding require type 2 conventional dendritic cells," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
    2. Dayakar Alti & Suresh Kumar Kalangi, 2018. "Trend of Regulatory T-Cells in the Pathogenesis of Leishmania Infection," Biomedical Journal of Scientific & Technical Research, Biomedical Research Network+, LLC, vol. 10(5), pages 8083-8085, November.
    3. Anna-Lena Geiselhöringer & Daphne Kolland & Arisha Johanna Patt & Linda Hammann & Amelie Köhler & Luisa Kreft & Nina Wichmann & Miriam Hils & Christiane Ruedl & Marc Riemann & Tilo Biedermann & David , 2024. "Dominant immune tolerance in the intestinal tract imposed by RelB-dependent migratory dendritic cells regulates protective type 2 immunity," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    4. Ricardo Monteiro & Tatiana B. Cereija & Rita Pombinho & Thijs Voskuilen & Jeroen D. C. Codée & Sandra Sousa & João H. Morais-Cabral & Didier Cabanes, 2025. "Molecular properties of the RmlT wall teichoic acid rhamnosyltransferase that modulates virulence in Listeria monocytogenes," Nature Communications, Nature, vol. 16(1), pages 1-17, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-54644-w. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.