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* Telethon Institute for Child Health Research, Centre for Child Health Research, University of Western Australia, West Perth, Australia; and
Laboratory of Immunohistochemistry and Immunopathology, Institute of Pathology, University of Oslo and The Pathology Clinic Rikshospitalet-Radiumhospitalet Medical Center, Oslo, Norway
An increase in the tempo of local dendritic cell (DC)-mediated immune surveillance is a recognized feature of the response to acute inflammation at airway mucosal surfaces, and transient up-regulation of the APC functions of these DC preceding their emigration to regional lymph nodes has recently been identified as an important trigger for T cell-mediated airway tissue damage in diseases such as asthma. In this study, using a rat model, we demonstrate that the kinetics of the airway mucosal DC (AMDC) response to challenge with heat-killed bacteria is considerably more rapid and as a consequence more effectively compartmentalized than that in recall responses to soluble Ag. Notably, Ag-bearing AMDC expressing full APC activity reach regional lymph nodes within 30 min of cessation of microbial exposure, and in contrast to recall responses to nonpathogenic Ags, there is no evidence of local expression of APC activity within the airway mucosa preceding DC emigration. We additionally demonstrate that, analogous to that reported in the gut, a subset of airway intraepithelial DC extend their processes into the airway lumen. This function is constitutively expressed within the AMDC population, providing a mechanism for continuous immune surveillance of the airway luminal surface in the absence of "danger" signals.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was supported by the National Health and Medical Research Council of Australia.
2 F.L.J. and D.H.S. are joint first authors.
3 Address correspondence and reprint requests to Professor Patrick G. Holt, Division of Cell Biology, Telethon Institute for Child Health Research, P.O. Box 855, West Perth WA 6872, Australia. E-mail address: patrick{at}ichr.uwa.edu.au
4 Abbreviations used in this paper: DC, dendritic cell; AMDC, airway mucosal DC; IEDC, intraepithelial DC; LN, lymph node; RLN, regional LN; NRS, normal rat serum; FSC, forward light scatter; SSC, side light scatter.
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