Bovine tuberculosis, caused by Mycobacterium bovis, is increasing in incidence and detailed knowledge of host-pathogen interactions in the natural host is essential to facilitate improved disease control through vaccination. Vaccination of neonatal calves with BCG has been shown to induce a significant level of protection from infection with M. bovis. Since neonatal vaccination of humans with BCG induces activation of innate lymphocytes such as NK cells, and neonatal calves have high circulating numbers of these cells, we hypothesised that these cells are important in the protective response induced by BCG.
Afferent and efferent lymphatic vessels draining the skin were surgically cannulated to access NK cells migrating from the site of BCG vaccination to the draining lymph node and those exiting the lymph node. CD2- NK cells were the principal subset of NK cells migrating from the skin to the draining lymph node and were also the main subset egressing from the lymph node to return to circulation.
NK cells play an important role in the shaping of adaptive immune responses through reciprocal interactions with antigen presenting cells. We therefore investigated the interactions of NK cells and BCG-infected monocyte derived dendritic cells (DC) to determine early innate mechanisms in the response to vaccination. CD2- NK cells were preferentially activated following culture with BCG-infected DC and were able to secrete high levels of IFNγ, a key cytokine in protective immunity to M. bovis that is also associated with Th1 biased immunity.
This study provides novel evidence to demonstrate that NK cells can re-circulate in steady-state conditions and that through interactions with antigen presenting cells they may be involved in driving protective adaptive immune responses during BCG vaccination.