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Zymosan by-passes the requirement for pulmonary antigen encounter in lung tissue-resident memory CD8+ T cell development

Mucosal Immunologyvolume 12pages403412 (2019) | Download Citation

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Abstract

Tissue-resident memory T cells (Trm) in the lung provide a frontline defence against respiratory pathogens. Vaccination models that lodge CD8+ Trm populations in the lung have been developed, all of which incorporate the local delivery of antigen plus adjuvant into the airways; a necessary approach as local cognate antigen recognition is required for optimal lung Trm development. Although pulmonary delivery of antigen is important for lung Trm development, the impact the co-administered adjuvant has on Trm differentiation is unclear. We show that while altering the adjuvant co-administered with the pulmonary delivered antigen does not impact the size of the lung Trm population, a particular adjuvant, zymosan, when administered into the airways without antigen can drive effector CD8+ T cells to differentiate into lung Trm. Zymosan signalling via dectin-1 receptor was sufficient to promote antigen-independent lung Trm development. When combined with an injectable influenza vaccination regime, intranasal zymosan delivery significantly boosted the size of the influenza virus-specific lung Trm population. Our results highlight that eliciting the appropriate local inflammatory milieu can by-pass the requirement for local antigen recognition in lung Trm development and emphasises that the appropriate selection of adjuvant can greatly improve vaccines that aim to elicit pulmonary Trm.

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Acknowledgements

We thank Dr. D. Jackson (Melbourne University, Australia) for TLR2 KO mice and Dr. S. Turner (Monash University, Australia) for influenza viruses (X31 and PR8). This work was supported by National Health and Medical Research Council of Australia to L.M.W.

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Author notes

  1. These authors contributed equally: Irina Caminschi, Mireille H. Lahoud.

Affiliations

  1. Infection and Immunity Program, Monash Biomedicine Discovery Institute and Department of Biochemistry and Molecular Biology, Monash University, Melbourne, VIC, Australia

    • Irina Caminschi
    •  & Mireille H. Lahoud
  2. Department of Microbiology and Immunology, The University of Melbourne, at the Peter Doherty Institute for Infection and Immunity, Melbourne, VIC, 3000, Australia

    • Angela Pizzolla
    •  & Linda M. Wakim

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Contributions

L.M.W, I.C. and M.H.L designed the project. A.P. and L.M.W performed the experiments and data analysis. L.M.W, I.C. and M.H.L contributed to writing the manuscript.

Conflict of interest

The authors declare that they have no conflict of interest.

Corresponding author

Correspondence to Linda M. Wakim.

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https://doi.org/10.1038/s41385-018-0124-2