Cotransfer of antigen and contextual information harmonizes peripheral and lymph node conventional dendritic cell activation

Pirillo, C. et al. (2023) Cotransfer of antigen and contextual information harmonizes peripheral and lymph node conventional dendritic cell activation. Science Immunology, 8(85), eadg8249. (doi: 10.1126/sciimmunol.adg8249) (PMID:37478193)

Abstract

T cell responses against infections and cancer are directed by conventional dendritic cells (cDCs) in lymph nodes distant from the site of challenge. Migratory cDCs, which travel from the tissue to the lymph node, not only drive initial T cell activation but also transfer antigen to lymph node–resident cDCs. These resident cells have essential roles defining the character of the resulting T cell response; however, it is unknown how they can appropriately process and present antigens to suitably direct responses given their spatial separation. Here, using a novel strain of influenza A and a modified melanoma model, we show that tissue and lymph node cDC activation is harmonized and that this is driven by cotransfer of contextual cues. In the tumor, incomplete cDC activation in the tumor microenvironment is mirrored by lymph node–resident cDCs, whereas during influenza infection, pathogen-associated molecular patterns cotransferred with antigen drive TLR signaling in resident cDCs and their subsequent robust activation. This cotransfer mechanism explains how individual antigens can be handled distinctly by resident cDCs and how signals driving poor tumoral cDC activation further impact the lymph node. Our findings clarify how tissue context dictates antigenic and, consequently, T cell fate in the lymph node.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Jasim, Dr Seema and Roberts, Dr Edward and Loney, Mr Colin and Zhao, Dr Huailong and Bravo-Blas, Dr Alberto and Donnelly, Dr Hannah and Shergold, Miss Amy and Hutchinson, Dr Edward and Devlin, Ryan and Shearer, Mr Patrick and Sims, Miss Anna and Perona-Wright, Dr Georgia and Pinto, Dr Rute
• Authors: Pirillo, C., Al Khalidi, S., Sims, A., Devlin, R., Zhao, H., Pinto, R., Jasim, S., Shearer, P. A., Shergold, A. L., Donnelly, H., Bravo-Blas, A., Loney, C., Perona-Wright, G., Hutchinson, E., and Roberts, E. W.
• College/School: College of Medical Veterinary and Life Sciences > School of Cancer Sciences; College of Medical Veterinary and Life Sciences > School of Infection & Immunity
• Journal Name: Science Immunology
• Publisher: American Association for the Advancement of Science
• ISSN: 2470-9468
• ISSN (Online): 2470-9468