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Blood, 1 September 2005, Vol. 106, No. 5, pp. 1843-1850.
Prepublished online as a Blood First Edition Paper on May 10, 2005; DOI 10.1182/blood-2005-03-1281.
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PHAGOCYTES
Neutrophils rapidly migrate via lymphatics after Mycobacterium bovis BCG intradermal vaccination and shuttle live bacilli to the draining lymph nodes
Valérie Abadie,
Edgar Badell,
Patrice Douillard,
Danielle Ensergueix,
Pieter J. M. Leenen,
Myriam Tanguy,
Laurence Fiette,
Sem Saeland,
Brigitte Gicquel, and
Nathalie Winter
From the Mycobacterial Genetics Unit and the Laboratory of Histotechnology and Pathology, Institut Pasteur, Paris, France; Laboratory for Immunological Research, Schering Plough Dardilly, France; and Department of Immunology, Erasmus Medical Center, Rotterdam, The Netherlands.
The early innate response after Mycobacterium bovis bacille Calmette-Guérin (BCG) vaccination is poorly characterized but probably decisive for subsequent protective immunity against tuberculosis. Therefore, we vaccinated mice with fluorescent BCG strains in the ear dorsum, as a surrogate of intradermal vaccination in humans. During the first 3 days, we tracked BCG host cells migrating out of the dermis to the auricular draining lymph nodes (ADLNs). Resident skin dendritic cells (DCs) or macrophages did not play a predominant role in early BCG capture and transport to ADLNs. The main BCG host cells rapidly recruited both in the dermis and ADLNs were neutrophils. Fluorescent green or red BCG strains injected into nonoverlapping sites were essentially sheltered by distinct neutrophils in the ADLN capsule, indicating that neutrophils had captured bacilli in peripheral tissue and transported them to the lymphoid organ. Strikingly, we observed BCG-infected neutrophils in the lumen of lymphatic vessels by confocal microscopy on ear dermis. Fluorescence-labeled neutrophils injected into the ears accumulated exclusively into the ipsilateral ADLN capsule after BCG vaccination. Thus, we provide in vivo evidence that neutrophils, like DCs or inflammatory monocytes, migrate via afferent lymphatics to lymphoid tissue and can shuttle live microorganisms. (Blood. 2005;106: 1843-1850)
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