title: Neutrophils rapidly migrate via lymphatics after Mycobacterium bovis BCG intradermal vaccination and shuttle live bacilli to the draining lymph nodes.
abstract: 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.
authors.affiliation: Mycobacterial Genetics Unit, Institut Pasteur, 25 rue du Docteur Roux, 7724 Paris Cedex 15, France.
authors.forename: Valérie
authors.initials: V
authors.lastname: Abadie
authors.forename: Edgar
authors.initials: E
authors.lastname: Badell
authors.forename: Patrice
authors.initials: P
authors.lastname: Douillard
authors.forename: Danielle
authors.initials: D
authors.lastname: Ensergueix
authors.forename: Pieter J M
authors.initials: PJ
authors.lastname: Leenen
authors.forename: Myriam
authors.initials: M
authors.lastname: Tanguy
authors.forename: Laurence
authors.initials: L
authors.lastname: Fiette
authors.forename: Sem
authors.initials: S
authors.lastname: Saeland
authors.forename: Brigitte
authors.initials: B
authors.lastname: Gicquel
authors.forename: Nathalie
authors.initials: N
authors.lastname: Winter
mesh_terms: D000818:Animals; D001500:BCG Vaccine / Q000008:administration & dosage* / Q000276:immunology; D002465:Cell Movement / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology; D004423:Ear; D005260:Female; D005456:Fluorescent Dyes / Q000737:chemistry; D007271:Injections, Intradermal; D008198:Lymph Nodes / Q000276:immunology*; D008208:Lymphatic System / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009163:Mycobacterium bovis / Q000276:immunology*; D018375:Neutrophil Activation; D009504:Neutrophils / Q000276:immunology* / Q000382:microbiology*; D013194:Staining and Labeling; D014018:Tissue Distribution
chemical_list: D001500:BCG Vaccine; D005456:Fluorescent Dyes