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Alveolar Macrophages Transport Pathogens to Lung Draining Lymph Nodes¹

Centre for Immunology and Infection, Hull York Medical School and Department of Biology, University of York, York, United Kingdom

The first step in inducing pulmonary adaptive immunity to allergens and airborne pathogens is Ag acquisition and transport to the lung draining lymph nodes (dLN). Dendritic cells (DC) sample the airways, and active transfer of Ag to the lung dLN is considered an exclusive property of migratory DC. However, alveolar macrophages (AM) are the first phagocytes to contact inhaled particulate matter. Although having well-defined immunoregulatory capabilities, AM are generally considered as restricted to the alveoli. We show that murine AM constitutively migrate from lung to dLN and that following exposure to Streptococcus pneumoniae, AM rapidly transport bacteria to this site. Thus AM, and not DC, appear responsible for the earliest delivery of these bacteria to secondary lymphoid tissue. The identification of this novel transport pathway has important consequences for our understanding of lung immunity and suggests more widespread roles for macrophages in the transport of Ags to lymphoid organs than previously appreciated.

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 study was funded by a Wellcome Trust grant to P.M.K. and A.C.K. and by grants from The Medical Research Council (to M.C.C. and P.M.K.).

A.K. conducted the research. M.C. contributed new analytical tools. All authors contributed to design of the research. A.K. and P.M.K. wrote the manuscript.

² Address correspondence and reprint requests to Dr. Alun Kirby, Centre for Immunology and Infection, Hull York Medical School and Department of Biology, University of York, Wentworth Way, York, YO10 5YW, U.K. E-mail address: ak510{at}york.ac.uk

³ Abbreviations used in this paper: AM, alveolar macrophage; BAL, bronchoalveolar lavage; DC, dendritic cell; dLN, draining lymph node; FSC, forward light scatter; LN, lymph node; mAM, migratory alveolar macrophage; SSC, side light scatter.