1. ¹The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia
2. ²Department of Medical Biology, Parkville, Victoria, Australia
3. ³The Cooperative Research Centre for Vaccine Technology, Parkville, Victoria, Australia
4. ⁴CSL Limited, Parkville, Victoria, Australia
5. ⁵Research Institute for Microbial Diseases, Osaka University, Osaka, Japan

Correspondence: Dr GT Belz, The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, Victoria 3050, Australia. E-mail: belz@wehi.edu.au; Dr JA Villadangos, E-mail: villadangos@wehi.edu.au

⁶Current address: Department of Molecular Oncology, Genentech Inc., 1 DNA Way, South San Francisco, CA 94080, USA.

⁷Current address: The Netherlands Cancer Institute, Amsterdam, The Netherlands.

⁸These authors contributed equally to this work.

Received 18 May 2007; Revised 27 August 2007; Accepted 27 September 2007; Published online 20 November 2007.

Abstract

Dendritic cells (DCs) play major roles in immunosurveillance. In peripheral tissues, 'immature' DCs are dedicated to capturing antigens. Detection of pathogens through Toll-like receptors (TLRs) triggers DC migration to the lymph nodes (LNs), where they acquire a 'mature' phenotype specialized at presenting antigens. However, DCs migrate from tissues and mature even in the absence of overt infections. This has been attributed to detection of commensal flora in the skin, the gut or other peripheral tissues in the steady state. To test this assumption, we have analyzed the DCs contained in the lymphoid organs of germ-free mice and of mice lacking the TLR adapter molecules, MyD88 and TRIF. We show that the proportion and expression of maturation markers in DC immigrants in the LNs of these mice are similar to those in normal mice. These results suggest that DC migration from tissues, followed by their phenotypic maturation, is regulated in the steady state by an inherent program of DC differentiation or by the release of low levels of inflammatory signals from normal tissues.