Abadie Valérie, Badell Edgar, Douillard Patrice, Ensergueix Danielle, Leenen Pieter J M, Tanguy Myriam, Fiette Laurence, Saeland Sem, Gicquel Brigitte, Winter Nathalie
Mycobacterial Genetics Unit, Institut Pasteur, 25 rue du Docteur Roux, 7724 Paris Cedex 15, France.
Blood. 2005 Sep 1;106(5):1843-50. doi: 10.1182/blood-2005-03-1281. Epub 2005 May 10.
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.
卡介苗(BCG)接种后的早期先天性反应特征尚不明确,但可能对随后针对结核病的保护性免疫起决定性作用。因此,我们用荧光卡介苗菌株对小鼠耳背部进行接种,以此模拟人类皮内接种。在头3天里,我们追踪了卡介苗宿主细胞从真皮迁移至耳引流淋巴结(ADLN)的过程。驻留皮肤树突状细胞(DC)或巨噬细胞在卡介苗早期捕获及转运至ADLN过程中并不起主要作用。在真皮和ADLN中迅速募集的主要卡介苗宿主细胞是中性粒细胞。注射到不重叠部位的绿色或红色荧光卡介苗菌株在ADLN被膜中基本上由不同的中性粒细胞隔离,这表明中性粒细胞在外周组织捕获杆菌并将其转运至淋巴器官。引人注目的是,通过耳真皮共聚焦显微镜观察,我们在淋巴管腔中发现了被卡介苗感染的中性粒细胞。卡介苗接种后,注射到耳部的荧光标记中性粒细胞仅聚集到同侧ADLN被膜中。因此,我们提供了体内证据,表明中性粒细胞与DC或炎性单核细胞一样,通过传入淋巴管迁移至淋巴组织,并且能够转运活的微生物。