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)
Do you have an account?
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
Article / Publication Details
Copyright / Drug Dosage / DisclaimerCopyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.