Long-Lasting Effects of BCG Vaccination on Both Heterologous Th1/Th17 Responses and Innate Trained ImmunityKleinnijenhuis J.a, b · Quintin J.a, b · Preijers F.c · Benn C.S.e · Joosten L.A.B.a, b · Jacobs C.a, b · van Loenhout J.d · Xavier R.J.f, g · Aaby P.e · van der Meer J.W.M.a, b · van Crevel R.a, b · Netea M.G.a, b
aDepartment of Medicine, bNijmegen Institute for Infection, Inflammation and Immunity (N4i) and cDepartment of Laboratory Medicine, Laboratory of Hematology, Radboud University Nijmegen Medical Centre, and dGGD, Nijmegen, The Netherlands; eResearch Center for Vitamins and Vaccines (CVIVA), Statens Serum Institut, Copenhagen, Denmark; fCenter for Computational and Integrative Biology and Gastrointestinal Unit, Massachusetts General Hospital, Harvard School of Medicine, Boston, Mass., and gBroad Institute of MIT and Harvard University, Cambridge, Mass., USA
Dr. Mihai G. Netea
Department of Medicine (463), Radboud University Nijmegen Medical Centre
Geert Grooteplein Zuid 8
NL-6525 GA Nijmegen (The Netherlands)
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We have recently shown that BCG (Bacillus Calmette-Guérin) vaccination in healthy volunteers induces epigenetic reprogramming of monocytes, leading to increased cytokine production in response to nonrelated pathogens for up to 3 months after vaccination. This phenomenon was named ‘trained immunity'. In the present study we assessed whether BCG was able to induce long-lasting effects on both trained immunity and heterologous T helper 1 (Th1) and Th17 immune responses 1 year after vaccination. The production of TNFα and IL-1β to mycobacteria or unrelated pathogens was higher after 2 weeks and 3 months postvaccination, but these effects were less pronounced 1 year after vaccination. However, monocytes recovered 1 year after vaccination had an increased expression of pattern recognition receptors such as CD14, Toll-like receptor 4 (TLR4) and mannose receptor, and this correlated with an increase in proinflammatory cytokine production after stimulation with the TLR4 ligand lipopolysaccharide. The heterologous production of Th1 (IFN-γ) and Th17 (IL-17 and IL-22) immune responses to nonmycobacterial stimulation remained strongly elevated even 1 year after BCG vaccination. In conclusion, BCG induces sustained changes in the immune system associated with a nonspecific response to infections both at the level of innate trained immunity and at the level of heterologous Th1/Th17 responses.
© 2013 S. Karger AG, Basel
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