Unresponsiveness to inhaled antigen is governed by conventional dendritic cells and overridden during infection by monocytes

James G. Bedford, Melanie Heinlein, Alexandra L. Garnham, Thi H.O. Nguyen, Tom Loudovaris, Chenghao Ge, Stuart I. Mannering, Michael Elliott, Stuart G. Tangye, Katherine Kedzierska, Daniel H.D. Gray, William R. Heath, Linda M. Wakim

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

Abstract

The nasal-associated lymphoid tissues (NALTs) are mucosal-associated lymphoid organs embedded in the submucosa of the nasal passage. NALTs represent a known site for the deposition of inhaled antigens, but little is known of the mechanisms involved in the induction of immunity within this lymphoid tissue. We find that during the steady state, conventional dendritic cells (cDCs) within the NALTs suppress T cell responses. These cDCs, which are also prevalent within human NALTs (tonsils/adenoids), express a unique transcriptional profile and inhibit T cell proliferation via contact-independent mechanisms that can be diminished by blocking the actions of reactive oxygen species and prostaglandin E2. Although the prevention of unrestrained immune activation to inhaled antigens appears to be the default function of NALT cDCs, inflammation after localized virus infection recruited monocyte-derived DCs (moDCs) to this region, which diluted out the suppressive DC pool, and permitted local T cell priming. Accommodating for inflammation-induced temporal changes in NALT DC composition and function, we developed an intranasal vaccine delivery system that coupled the recruitment of moDCs with the sustained release of antigen into the NALTs, and we were able to substantially improve T cell responses after intranasal immunization. Thus, homeostasis and immunity to inhaled antigens is tuned by inflammatory signals that regulate the balance between conventional and moDC populations within the NALTs.

Original languageEnglish (US)
Article numbereabb5439
JournalScience immunology
Volume5
Issue number52
DOIs
StatePublished - Oct 16 2020
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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