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

• Published in: Mucosal immunology Vol. 12; no. 2; pp. 403 - 412
• Main Authors: Caminschi, Irina, Lahoud, Mireille H., Pizzolla, Angela, Wakim, Linda M.
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01.03.2019; Elsevier Limited
• Subjects: Adjuvants, Immunologic; Allergology; Animals; Antibodies; Antigens; Antigens - immunology; Biomedical and Life Sciences; Biomedicine; CD8 antigen; CD8-Positive T-Lymphocytes - immunology; Cell Differentiation; Cells, Cultured; Cellular Microenvironment; Effector cells; Gastroenterology; Humans; Immunization; Immunologic Memory; Immunological memory; Immunology; Inflammation; Influenza; Influenza A virus - immunology; Influenza Vaccines - immunology; Influenza, Human - immunology; Lectins, C-Type - metabolism; Lung - immunology; Lungs; Lymphocyte Activation; Lymphocytes T; Memory cells; Mice; Mice, Transgenic; Orthomyxoviridae Infections - immunology; Respiratory diseases; Signal Transduction; T-Lymphocytes, Regulatory - immunology; Vaccination; Zymosan - administration & dosage; Zymosan - immunology
• ISSN: 1933-0219; 1935-3456
• DOI: 10.1038/s41385-018-0124-2

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.