Neutrophils rapidly migrate via lymphatics after Mycobacterium bovis BCG intradermal vaccination and shuttle live bacilli to the draining lymph nodes

The early innate response after Mycobac- terium bovis bacille Calmette-Guerin (BCG) vaccination is poorly character- ized but probably decisive for subse- quent protective immunity against tuber- culosis. 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 migrat- ing 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 neu- trophils. Fluorescent green or red BCG strains injected into nonoverlapping sites were essentially sheltered by distinct neu- trophils in the ADLN capsule, indicating that neutrophils had captured bacilli in peripheral tissue and transported them to the lymphoid organ. Strikingly, we ob- served 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 ipsilat- eral ADLN capsule after BCG vaccination. Thus, we provide in vivo evidence that neutrophils, like DCs or inflammatory monocytes, migrate via afferent lymphat- ics to lymphoid tissue and can shuttle live microorganisms. (Blood. 2005;106: 1843-1850)