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, Thomas Loudovaris, Chenghao Ge, Stuart I. Mannering, Michael Elliott, Stuart G. Tangye, Katherine Kedzierska, Daniel H.D. Gray, William R. Heath, Linda M. Wakim
Abstract
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.