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2. Dimethyl itaconate induces long-term innate immune responses and confers protection against infection

Author

Ferreira, Anaísa V., Kostidis, Sarantos, Groh, Laszlo A., Koeken, Valerie A.C.M., Bruno, Mariolina, Baydemir, Ilayda, Kilic, Gizem, Bulut, Özlem, Andriopoulou, Theano, Spanou, Victoria, Synodinou, Kalliopi D., Gkavogianni, Theologia, Moorlag, Simone J.C.F.M., Charlotte de Bree, L., Mourits, Vera P., Matzaraki, Vasiliki, Koopman, Werner J.H., van de Veerdonk, Frank L., Renieris, Georgios, Giera, Martin, Giamarellos-Bourboulis, Evangelos J., Novakovic, Boris, and Domínguez-Andrés, Jorge

Published
2023
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4. Safety and COVID-19 Symptoms in Individuals Recently Vaccinated with BCG: a Retrospective Cohort Study

Author

Moorlag, Simone J.C.F.M., van Deuren, Rosanne C., van Werkhoven, Cornelis H., Jaeger, Martin, Debisarun, Priya, Taks, Esther, Mourits, Vera P., Koeken, Valerie A.C.M., de Bree, L. Charlotte J., ten Doesschate, Thijs, Cleophas, Maartje C., Smeekens, Sanne, Oosting, Marije, van de Veerdonk, Frank L., Joosten, Leo A.B., ten Oever, Jaap, van der Meer, Jos W.M., Curtis, Nigel, Aaby, Peter, Stabell-Benn, Christine, Giamarellos-Bourboulis, Evangelos J., Bonten, Marc, van Crevel, Reinout, and Netea, Mihai G.

Published
2020
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5. Circadian rhythm influences induction of trained immunity by BCG vaccination

Author

de Bree, L. Charlotte J., Mourits, Vera P., Koeken, Valerie A.C.M., Moorlag, Simone J.C.F.M., Janssen, Robine, Folkman, Lukas, Barreca, Daniele, Krausgruber, Thomas, Fife-Gernedl, Victoria, Novakovic, Boris, Arts, Rob J.W., Dijkstra, Helga, Lemmers, Heidi, Bock, Christoph, Joosten, Leo A.B., van Crevel, Reinout, Benn, Christine S., and Netea, Mihai G.

Subjects
Tuberculosis vaccines -- Comparative analysis -- Health aspects, Infants -- Health aspects -- Comparative analysis, Infant mortality -- Health aspects -- Comparative analysis, BCG -- Comparative analysis -- Health aspects, Staphylococcus aureus -- Health aspects -- Comparative analysis, Antitubercular agents -- Health aspects -- Comparative analysis, Medical research -- Comparative analysis -- Health aspects, Infection -- Health aspects -- Comparative analysis, Vaccination -- Health aspects -- Comparative analysis, Tuberculosis -- Comparative analysis -- Health aspects, EDTA -- Comparative analysis -- Health aspects, Health care industry
Abstract

BACKGROUND. The antituberculosis vaccine bacillus Calmette-Guerin (BCG) reduces overall infant mortality. Induction of innate immune memory, also termed trained immunity, contributes toward protection against heterologous infections. Since immune cells display oscillations in numbers and function throughout the day, we investigated the effect of BCG administration time on the induction of trained immunity. METHODS. Eighteen volunteers were vaccinated with BCG at 6 pm and compared with 36 age- and sex-matched volunteers vaccinated between 8 am and 9 am. Peripheral blood mononuclear cells were stimulated with Staphylococcus aureus and Mycobacterium tuberculosis before, as well as 2 weeks and 3 months after, BCG vaccination. Cytokine production was measured to assess the induction of trained immunity and adaptive responses, respectively. Additionally, the influence of vaccination time on induction of trained immunity was studied in an independent cohort of 302 individuals vaccinated between 8 am and 12 pm with BCG. RESULTS. Compared with evening vaccination, morning vaccination elicited both a stronger trained immunity and adaptive immune phenotype. In a large cohort of 302 volunteers, early morning vaccination resulted in a superior cytokine production capacity compared with later morning. A cellular, rather than soluble, substrate of the circadian effect of BCG vaccination was demonstrated by the enhanced capacity to induce trained immunity in vitro in morning- compared with evening-isolated monocytes. CONCLUSIONS. BCG vaccination in the morning induces stronger trained immunity and adaptive responses compared with evening vaccination. Future studies should take vaccine administration time into account when studying specific and nonspecific effects of vaccines; early morning should be the preferred moment of BCG administration. FUNDING. The Netherlands Organization for Scientific Research, the European Research Council, and the Danish National Research Foundation., Introduction The antituberculosis vaccine bacillus Calmette-Guerin (BCG) has the highest vaccine coverage worldwide (1). BCG protects primarily against disseminated tuberculosis (TB) in children (2), whereas protection against pulmonary TB in [...]

Published
2020
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6. BCG vaccination in humans inhibits systemic inflammation in a sex-dependent manner

Author

Koeken, Valerie A.C.M., de Bree, L. Charlotte J., Mourits, Vera P., Moorlag, Simone J.C.F.M., Walk, Jona, Cirovic, Branko, Arts, Rob J.W., Jaeger, Martin, Dijkstra, Helga, Lemmers, Heidi, Joosten, Leo A.B., Benn, Christine S., van Crevel, Reinout, and Netea, Mihai G.

Subjects
Tuberculosis vaccines -- Evaluation, BCG -- Evaluation, Inflammation -- Health aspects, Antitubercular agents -- Evaluation, Vaccination -- Health aspects, Proteins -- Health aspects, Health care industry
Abstract

BACKGROUND. Induction of innate immune memory, also termed trained immunity, by the antituberculosis vaccine bacillus Calmette-Guerin (BCG) contributes to protection against heterologous infections. However, the overall impact of BCG vaccination on the inflammatory status of an individual is not known; while induction of trained immunity may suggest increased inflammation, BCG vaccination has been epidemiologically associated with a reduced incidence of inflammatory and allergic diseases. METHODS. We investigated the impact of BCG (BCG-Bulgaria, InterVax) vaccination on systemic inflammation in a cohort of 303 healthy volunteers, as well as the effect of the inflammatory status on the response to vaccination. A targeted proteome platform was used to measure circulating inflammatory proteins before and after BCG vaccination, while ex vivo Mycobacterium tuberculosis- and Staphylococcus aureus-induced cytokine responses in peripheral blood mononuclear cells were used to assess trained immunity. RESULTS. While BCG vaccination enhanced cytokine responses to restimulation, it reduced systemic inflammation. This effect was validated in 3 smaller cohorts, and was much stronger in men than in women. In addition, baseline circulating inflammatory markers were associated with ex vivo cytokine responses (trained immunity) after BCG vaccination. CONCLUSION. The capacity of BCG to enhance microbial responsiveness while dampening systemic inflammation should be further explored for potential therapeutic applications. FUNDING. Netherlands Organization for Scientific Research, European Research Council, and the Danish National Research Foundation., Introduction The traditional view of vaccines is that they protect against a particular infection by induction of long-lasting specific adaptive immune memory. The discovery of the induction of nonspecific innate [...]

Published
2020
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7. Rewiring of glucose metabolism defines trained immunity induced by oxidized low-density lipoprotein

Author

Keating, Samuel T., Groh, Laszlo, Thiem, Kathrin, Bekkering, Siroon, Li, Yang, Matzaraki, Vasiliki, van der Heijden, Charlotte D. C. C., van Puffelen, Jelmer H., Lachmandas, Ekta, Jansen, Trees, Oosting, Marije, de Bree, L. Charlotte J., Koeken, Valerie A. C. M., Moorlag, Simone J. C. F. M., Mourits, Vera P., van Diepen, Janna, Strienstra, Rinke, Novakovic, Boris, Stunnenberg, Hendrik G., van Crevel, Reinout, Joosten, Leo A. B., Netea, Mihai G., and Riksen, Niels P.

Published
2020
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9. Integration of metabolomics, genomics, and immune phenotypes reveals the causal roles of metabolites in disease

Author

Chu, Xiaojing, Jaeger, Martin, Beumer, Joep, Bakker, Olivier B., Aguirre-Gamboa, Raul, Oosting, Marije, Smeekens, Sanne P., Moorlag, Simone, Mourits, Vera P., Koeken, Valerie A. C. M., de Bree, Charlotte, Jansen, Trees, Mathews, Ian T., Dao, Khoi, Najhawan, Mahan, Watrous, Jeramie D., Joosten, Irma, Sharma, Sonia, Koenen, Hans J. P. M., Withoff, Sebo, Jonkers, Iris H., Netea-Maier, Romana T., Xavier, Ramnik J., Franke, Lude, Xu, Cheng-Jian, Joosten, Leo A. B., Sanna, Serena, Jain, Mohit, Kumar, Vinod, Clevers, Hans, Wijmenga, Cisca, Netea, Mihai G., and Li, Yang

Published
2021
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10. Correction to: Rewiring of glucose metabolism defines trained immunity induced by oxidized low-density lipoprotein

Author

Keating, Samuel T., Groh, Laszlo, Thiem, Kathrin, Bekkering, Siroon, Li, Yang, Matzaraki, Vasiliki, van der Heijden, Charlotte D. C. C., van Puffelen, Jelmer H., Lachmandas, Ekta, Jansen, Trees, Oosting, Marije, de Bree, L. Charlotte J., Koeken, Valerie A. C. M., Moorlag, Simone J. C. F. M., Mourits, Vera P., van Diepen, Janna, Stienstra, Rinke, Novakovic, Boris, Stunnenberg, Hendrik G., van Crevel, Reinout, Joosten, Leo A. B., Netea, Mihai G., and Riksen, Niels P.

Published
2020
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11. Plasma metabolome predicts trained immunity responses after antituberculosis BCG vaccination

Author

Koeken, Valerie A. C. M., primary, Qi, Cancan, additional, Mourits, Vera P., additional, de Bree, L. Charlotte J., additional, Moorlag, Simone J. C. F. M., additional, Sonawane, Vidhisha, additional, Lemmers, Heidi, additional, Dijkstra, Helga, additional, Joosten, Leo A. B., additional, van Laarhoven, Arjan, additional, Xu, Cheng-Jian, additional, van Crevel, Reinout, additional, Netea, Mihai G., additional, and Li, Yang, additional

Published
2022
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12. The Genetic Risk for COVID-19 Severity Is Associated With Defective Immune Responses

Author

Kuijpers, Yunus, primary, Chu, Xiaojing, additional, Jaeger, Martin, additional, Moorlag, Simone J. C. F. M., additional, Koeken, Valerie A. C. M., additional, Zhang, Bowen, additional, Nooijer, Aline de, additional, Grondman, Inge, additional, Gupta, Manoj Kumar, additional, Janssen, Nico, additional, Mourits, Vera P., additional, de Bree, L. Charlotte J., additional, de Mast, Quirijn, additional, van de Veerdonk, Frank L., additional, Joosten, Leo A. B., additional, Li, Yang, additional, Netea, Mihai G., additional, and Xu, Cheng-Jian, additional

Published
2022
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13. Immune modulatory effects of progesterone on oxLDL-induced trained immunity in monocytes

Author

Groh, Laszlo A, primary, Verel, Dagmar E, additional, van der Heijden, Charlotte D C C, additional, Matzaraki, Vasiliki, additional, Moorlag, Simone J C F M, additional, de Bree, L Charlotte, additional, Koeken, Valerie A C M, additional, Mourits, Vera P, additional, Keating, Samuel T, additional, van Puffelen, Jelmer H, additional, Joosten, Leo A B, additional, Netea, Mihai G, additional, and Riksen, Niels P, additional

Published
2022
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14. The Immunological Factors Predisposing to Severe Covid-19 Are Already Present in Healthy Elderly and Men

Author

Kilic, Gizem, primary, Bulut, Ozlem, additional, Jaeger, Martin, additional, ter Horst, Rob, additional, Koeken, Valerie A. C. M., additional, Moorlag, Simone J. C. F. M., additional, Mourits, Vera P., additional, de Bree, Charlotte, additional, Domínguez-Andrés, Jorge, additional, Joosten, Leo A. B., additional, and Netea, Mihai G., additional

Published
2021
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15. induction of trained immunity in adherent human monocytes

Author

Domínguez-Andrés, Jorge, Arts, Rob J W, Bekkering, Siroon, Bahrar, Harsh, Blok, Bastiaan A, de Bree, L Charlotte J, Bruno, Mariolina, Bulut, Özlem, Debisarun, Priya A, Dijkstra, Helga, Cristina Dos Santos, Jéssica, Ferreira, Anaísa V, Flores-Gomez, Daniela, Groh, Laszlo A, Grondman, Inge, Helder, Leonie, Jacobs, Cor, Jacobs, Liesbeth, Jansen, Trees, Kilic, Gizem, Klück, Viola, Koeken, Valerie A C M, Lemmers, Heidi, Moorlag, Simone J C F M, Mourits, Vera P, van Puffelen, Jelmer H, Rabold, Katrin, Röring, Rutger J, Rosati, Diletta, Tercan, Helin, van Tuijl, Julia, Quintin, Jessica, van Crevel, Reinout, Riksen, Niels P, Joosten, Leo A B, Netea, Mihai G, and CiiM, Zentrum für individualisierte Infektionsmedizin, Feodor-Lynen-Str.7, 30625 Hannover.

Subjects
Cell biology, Cell isolation, Immunology, Cell-based assays
Abstract

A growing number of studies show that innate immune cells can undergo functional reprogramming, facilitating a faster and enhanced response to heterologous secondary stimuli. This concept has been termed "trained immunity." We outline here a protocol to recapitulate this in vitro using adherent monocytes from consecutive isolation of peripheral blood mononuclear cells. The induction of trained immunity and the associated functional reprogramming of monocytes is described in detail using β-glucan (from Candida albicans) and Bacillus Calmette-Guérin as examples. For complete details on the use and execution of this protocol, please refer to Repnik et al. (2003) and Bekkering et al. (2016).

Published
2021

18. The role of sirtuin 1 on the induction of trained immunity

Author

Mourits, Vera P., Helder, Leonie S., Matzaraki, Vasiliki, Koeken, Valerie A. C. M., Groh, Laszlo, de Bree, L. Charlotte J., Moorlag, Simone J. C. F. M., van der Heijden, Charlotte D. C. C., Keating, Samuel T., van Puffelen, Jelmer H., Jaeger, Martin, Joosten, Leo A. B., Netea, Mihai G., Mourits, Vera P., Helder, Leonie S., Matzaraki, Vasiliki, Koeken, Valerie A. C. M., Groh, Laszlo, de Bree, L. Charlotte J., Moorlag, Simone J. C. F. M., van der Heijden, Charlotte D. C. C., Keating, Samuel T., van Puffelen, Jelmer H., Jaeger, Martin, Joosten, Leo A. B., and Netea, Mihai G.

Abstract

Sirtuin 1 (SIRT1) has been described to modify immune responses by modulation of gene transcription. As transcriptional reprogramming is the molecular substrate of trained immunity, a de facto innate immune memory, we investigated the role of SIRT1 in the induction of trained immunity. We identified various SIRT1 genetic single nucleotide polymorphisms affecting innate and adaptive cytokine production of human peripheral blood mononuclear cells (PBMCs) in response to various stimuli on the one hand, and in vitro induction of trained immunity on the other hand. Furthermore, inhibition of SIRT1 upregulated pro-inflammatory innate cytokine production upon stimulation of PBMCs. However, inhibition of SIRT1 in vitro had no effect on cytokine responses upon induction of trained immunity, while activation of SIRT1 mildly modified trained immunity responses. In conclusion, SIRT1 modifies innate cytokine production by PBMCs in response to various microbes, but has only a secondary role for BCG and β-glucan-induced trained immunity responses.

Published
2021

19. Integration of metabolomics, genomics, and immune phenotypes reveals the causal roles of metabolites in disease

Author

Hubrecht Institute with UMC, Chu, Xiaojing, Jaeger, Martin, Beumer, Joep, Bakker, Olivier B., Aguirre-Gamboa, Raul, Oosting, Marije, Smeekens, Sanne P., Moorlag, Simone, Mourits, Vera P., Koeken, Valerie A.C.M., de Bree, Charlotte, Jansen, Trees, Mathews, Ian T., Dao, Khoi, Najhawan, Mahan, Watrous, Jeramie D., Joosten, Irma, Sharma, Sonia, Koenen, Hans J.P.M., Withoff, Sebo, Jonkers, Iris H., Netea-Maier, Romana T., Xavier, Ramnik J., Franke, Lude, Xu, Cheng Jian, Joosten, Leo A.B., Sanna, Serena, Jain, Mohit, Kumar, Vinod, Clevers, Hans, Wijmenga, Cisca, Netea, Mihai G., Li, Yang, Hubrecht Institute with UMC, Chu, Xiaojing, Jaeger, Martin, Beumer, Joep, Bakker, Olivier B., Aguirre-Gamboa, Raul, Oosting, Marije, Smeekens, Sanne P., Moorlag, Simone, Mourits, Vera P., Koeken, Valerie A.C.M., de Bree, Charlotte, Jansen, Trees, Mathews, Ian T., Dao, Khoi, Najhawan, Mahan, Watrous, Jeramie D., Joosten, Irma, Sharma, Sonia, Koenen, Hans J.P.M., Withoff, Sebo, Jonkers, Iris H., Netea-Maier, Romana T., Xavier, Ramnik J., Franke, Lude, Xu, Cheng Jian, Joosten, Leo A.B., Sanna, Serena, Jain, Mohit, Kumar, Vinod, Clevers, Hans, Wijmenga, Cisca, Netea, Mihai G., and Li, Yang

Published
2021

20. Glutathione Metabolism Contributes to the Induction of Trained Immunity

Author

Ferreira, Anaisa V., primary, Koeken, Valerie A. C. M., additional, Matzaraki, Vasiliki, additional, Kostidis, Sarantos, additional, Alarcon-Barrera, Juan Carlos, additional, de Bree, L. Charlotte J., additional, Moorlag, Simone J. C. F. M., additional, Mourits, Vera P., additional, Novakovic, Boris, additional, Giera, Martin A., additional, Netea, Mihai G., additional, and Domínguez-Andrés, Jorge, additional

Published
2021
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21. The effect of BCG vaccination on alveolar macrophages obtained from induced sputum from healthy volunteers

Author

Koeken, Valerie A. C. M., van der Pasch, Eva S., Leijte, Guus P., Mourits, Vera P., de Bree, L. Charlotte J., Moorlag, Simone J. C. F. M., Budnick, Isadore, Idh, Nina, Lerm, Maria, Kox, Matthijs, van Laarhoven, Arjan, Netea, Mihai G., van Crevel, Reinout, Koeken, Valerie A. C. M., van der Pasch, Eva S., Leijte, Guus P., Mourits, Vera P., de Bree, L. Charlotte J., Moorlag, Simone J. C. F. M., Budnick, Isadore, Idh, Nina, Lerm, Maria, Kox, Matthijs, van Laarhoven, Arjan, Netea, Mihai G., and van Crevel, Reinout

Abstract

The anti-tuberculosis vaccine Bacillus Calmette-Guerin (BCG) is able to boost innate immune responses through a process called trained immunity. It is hypothesized that BCG-induced trained immunity contributes to protection against Mycobacterium tuberculosis infection. Since alveolar macrophages are the first cell type to encounter M. tuberculosis upon infection, we aimed to investigate the immunomodulatory effects of BCG vaccination on alveolar macrophages. Searching for a less-invasive method than bronchoalveolar lavage, we optimized the isolation of alveolar macrophages from induced sputum of healthy volunteers. Viable alveolar macrophages could be successfully isolated from induced sputum and showed signs of activation already upon retrieval. Further flow cytometric analyses revealed that at baseline, higher expression levels of activation markers were observed on the alveolar macrophages of smokers compared to non-smokers. In addition, BCG vaccination resulted in decreased expression of the activation markers CD11b and HLA-DR on alveolar macrophages. Future studies should evaluate the functional consequences of this reduced activation of alveolar macrophages after BCG vaccination., Funding Agencies|Netherlands Organization for Scientific ResearchNetherlands Organization for Scientific Research (NWO); National Institute Of Allergy And Infectious Diseases of the National Institutes of Health, ULTIMATE project [1R01AI145781-01]

Published
2020
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22. Trained Immunity-Promoting Nanobiologic Therapy Suppresses Tumor Growth and Potentiates Checkpoint Inhibition

Author

In Vivo NMR ISI, MMB Research line 3a, Brain, Circulatory Health, Priem, Bram, van Leent, Mandy M.T., Teunissen, Abraham J.P., Sofias, Alexandros Marios, Mourits, Vera P., Willemsen, Lisa, Klein, Emma D., Oosterwijk, Roderick S., Meerwaldt, Anu E., Munitz, Jazz, Prévot, Geoffrey, Vera Verschuur, Anna, Nauta, Sheqouia A., van Leeuwen, Esther M., Fisher, Elizabeth L., de Jong, Karen A.M., Zhao, Yiming, Toner, Yohana C., Soultanidis, Georgios, Calcagno, Claudia, Bomans, Paul H.H., Friedrich, Heiner, Sommerdijk, Nico, Reiner, Thomas, Duivenvoorden, Raphaël, Zupančič, Eva, Di Martino, Julie S., Kluza, Ewelina, Rashidian, Mohammad, Ploegh, Hidde L., Dijkhuizen, Rick M., Hak, Sjoerd, Pérez-Medina, Carlos, Bravo-Cordero, Jose Javier, de Winther, Menno P.J., Joosten, Leo A.B., van Elsas, Andrea, Fayad, Zahi A., Rialdi, Alexander, Torre, Denis, Guccione, Ernesto, Ochando, Jordi, Netea, Mihai G., Griffioen, Arjan W., Mulder, Willem J.M., In Vivo NMR ISI, MMB Research line 3a, Brain, Circulatory Health, Priem, Bram, van Leent, Mandy M.T., Teunissen, Abraham J.P., Sofias, Alexandros Marios, Mourits, Vera P., Willemsen, Lisa, Klein, Emma D., Oosterwijk, Roderick S., Meerwaldt, Anu E., Munitz, Jazz, Prévot, Geoffrey, Vera Verschuur, Anna, Nauta, Sheqouia A., van Leeuwen, Esther M., Fisher, Elizabeth L., de Jong, Karen A.M., Zhao, Yiming, Toner, Yohana C., Soultanidis, Georgios, Calcagno, Claudia, Bomans, Paul H.H., Friedrich, Heiner, Sommerdijk, Nico, Reiner, Thomas, Duivenvoorden, Raphaël, Zupančič, Eva, Di Martino, Julie S., Kluza, Ewelina, Rashidian, Mohammad, Ploegh, Hidde L., Dijkhuizen, Rick M., Hak, Sjoerd, Pérez-Medina, Carlos, Bravo-Cordero, Jose Javier, de Winther, Menno P.J., Joosten, Leo A.B., van Elsas, Andrea, Fayad, Zahi A., Rialdi, Alexander, Torre, Denis, Guccione, Ernesto, Ochando, Jordi, Netea, Mihai G., Griffioen, Arjan W., and Mulder, Willem J.M.

Published
2020

23. Safety and COVID-19 Symptoms in Individuals Recently Vaccinated with BCG: a Retrospective Cohort Study

Author

Epi Infectieziekten Team 1, Infection & Immunity, JC onderzoeksprogramma Infectieziekten, Epi Infectieziekten, MMB, Moorlag, Simone J C F M, van Deuren, Rosanne C, van Werkhoven, Cornelis H, Jaeger, Martin, Debisarun, Priya, Taks, Esther, Mourits, Vera P, Koeken, Valerie A C M, de Bree, L Charlotte J, Ten Doesschate, Thijs, Cleophas, Maartje C, Smeekens, Sanne, Oosting, Marije, van de Veerdonk, Frank L, Joosten, Leo A B, Ten Oever, Jaap, van der Meer, Jos W M, Curtis, Nigel, Aaby, Peter, Stabell-Benn, Christine, Giamarellos-Bourboulis, Evangelos J, Bonten, Marc, van Crevel, Reinout, Netea, Mihai G, Epi Infectieziekten Team 1, Infection & Immunity, JC onderzoeksprogramma Infectieziekten, Epi Infectieziekten, MMB, Moorlag, Simone J C F M, van Deuren, Rosanne C, van Werkhoven, Cornelis H, Jaeger, Martin, Debisarun, Priya, Taks, Esther, Mourits, Vera P, Koeken, Valerie A C M, de Bree, L Charlotte J, Ten Doesschate, Thijs, Cleophas, Maartje C, Smeekens, Sanne, Oosting, Marije, van de Veerdonk, Frank L, Joosten, Leo A B, Ten Oever, Jaap, van der Meer, Jos W M, Curtis, Nigel, Aaby, Peter, Stabell-Benn, Christine, Giamarellos-Bourboulis, Evangelos J, Bonten, Marc, van Crevel, Reinout, and Netea, Mihai G

Published
2020

24. A modular approach toward producing nanotherapeutics targeting the innate immune system

Author

van Leent, Mandy M. T., primary, Meerwaldt, Anu E., additional, Berchouchi, Alexandre, additional, Toner, Yohana C., additional, Burnett, Marianne E., additional, Klein, Emma D., additional, Verschuur, Anna Vera D., additional, Nauta, Sheqouia A., additional, Munitz, Jazz, additional, Prévot, Geoffrey, additional, van Leeuwen, Esther M., additional, Ordikhani, Farideh, additional, Mourits, Vera P., additional, Calcagno, Claudia, additional, Robson, Philip M., additional, Soultanidis, George, additional, Reiner, Thomas, additional, Joosten, Rick R. M., additional, Friedrich, Heiner, additional, Madsen, Joren C., additional, Kluza, Ewelina, additional, van der Meel, Roy, additional, Joosten, Leo A. B., additional, Netea, Mihai G., additional, Ochando, Jordi, additional, Fayad, Zahi A., additional, Pérez-Medina, Carlos, additional, Mulder, Willem J. M., additional, and Teunissen, Abraham J. P., additional

Published
2021
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25. In vitro induction of trained immunity in adherent human monocytes

Author

Domínguez-Andrés, Jorge, primary, Arts, Rob J.W., additional, Bekkering, Siroon, additional, Bahrar, Harsh, additional, Blok, Bastiaan A., additional, de Bree, L. Charlotte J., additional, Bruno, Mariolina, additional, Bulut, Özlem, additional, Debisarun, Priya A., additional, Dijkstra, Helga, additional, Cristina dos Santos, Jéssica, additional, Ferreira, Anaísa V., additional, Flores-Gomez, Daniela, additional, Groh, Laszlo A., additional, Grondman, Inge, additional, Helder, Leonie, additional, Jacobs, Cor, additional, Jacobs, Liesbeth, additional, Jansen, Trees, additional, Kilic, Gizem, additional, Klück, Viola, additional, Koeken, Valerie A.C.M., additional, Lemmers, Heidi, additional, Moorlag, Simone J.C.F.M., additional, Mourits, Vera P., additional, van Puffelen, Jelmer H., additional, Rabold, Katrin, additional, Röring, Rutger J., additional, Rosati, Diletta, additional, Tercan, Helin, additional, van Tuijl, Julia, additional, Quintin, Jessica, additional, van Crevel, Reinout, additional, Riksen, Niels P., additional, Joosten, Leo A.B., additional, and Netea, Mihai G., additional

Published
2021
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26. Thyrotrophin and thyroxine support immune homeostasis in humans

Author

Jaeger, Martin, primary, Sloot, Yvette J.E, additional, Horst, Rob Ter, additional, Chu, Xiaojing, additional, Koenen, Hans J.P.M., additional, Koeken, Valerie A.C.M., additional, Moorlag, Simone J.C.F.M., additional, de Bree, Charlotte J., additional, Mourits, Vera P., additional, Lemmers, Heidi, additional, Dijkstra, Helga, additional, Medici, Marco, additional, van Herwaarden, Antonius E., additional, Joosten, Irma, additional, Joosten, Leo A.B., additional, Li, Yang, additional, Smit, Johannes W.A., additional, Netea, Mihai G., additional, and Netea‐Maier, Romana T., additional

Published
2021
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27. Lysine methyltransferase G9a is an important modulator of trained immunity

Author

Mourits, Vera P, primary, Puffelen, Jelmer H, additional, Novakovic, Boris, additional, Bruno, Mariolina, additional, Ferreira, Anaísa V, additional, Arts, Rob JW, additional, Groh, Laszlo, additional, Crișan, Tania O, additional, Zwaag, Jelle, additional, Jentho, Elisa, additional, Kox, Matthijs, additional, Pickkers, Peter, additional, Veerdonk, Frank L, additional, Weis, Sebastian, additional, Oosterwijk, Egbert, additional, Vermeulen, Sita H, additional, Netea, Mihai G, additional, and Joosten, Leo AB, additional

Published
2021
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28. BCG Vaccination Induces Long-Term Functional Reprogramming of Human Neutrophils

Author

Moorlag, Simone J.C.F.M., primary, Rodriguez-Rosales, Yessica Alina, additional, Gillard, Joshua, additional, Fanucchi, Stephanie, additional, Theunissen, Kate, additional, Novakovic, Boris, additional, de Bont, Cynthia M., additional, Negishi, Yutaka, additional, Fok, Ezio T., additional, Kalafati, Lydia, additional, Verginis, Panayotis, additional, Mourits, Vera P., additional, Koeken, Valerie A.C.M., additional, de Bree, L. Charlotte J., additional, Pruijn, Ger J.M., additional, Fenwick, Craig, additional, van Crevel, Reinout, additional, Joosten, Leo A.B., additional, Joosten, Irma, additional, Koenen, Hans, additional, Mhlanga, Musa M., additional, Diavatopoulos, Dimitri A., additional, Chavakis, Triantafyllos, additional, and Netea, Mihai G., additional

Published
2020
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29. Trained Immunity-Promoting Nanobiologic Therapy Suppresses Tumor Growth and Potentiates Checkpoint Inhibition

Author

Priem, Bram, primary, van Leent, Mandy M.T., additional, Teunissen, Abraham J.P., additional, Sofias, Alexandros Marios, additional, Mourits, Vera P., additional, Willemsen, Lisa, additional, Klein, Emma D., additional, Oosterwijk, Roderick S., additional, Meerwaldt, Anu E., additional, Munitz, Jazz, additional, Prévot, Geoffrey, additional, Vera Verschuur, Anna, additional, Nauta, Sheqouia A., additional, van Leeuwen, Esther M., additional, Fisher, Elizabeth L., additional, de Jong, Karen A.M., additional, Zhao, Yiming, additional, Toner, Yohana C., additional, Soultanidis, Georgios, additional, Calcagno, Claudia, additional, Bomans, Paul H.H., additional, Friedrich, Heiner, additional, Sommerdijk, Nico, additional, Reiner, Thomas, additional, Duivenvoorden, Raphaël, additional, Zupančič, Eva, additional, Di Martino, Julie S., additional, Kluza, Ewelina, additional, Rashidian, Mohammad, additional, Ploegh, Hidde L., additional, Dijkhuizen, Rick M., additional, Hak, Sjoerd, additional, Pérez-Medina, Carlos, additional, Bravo-Cordero, Jose Javier, additional, de Winther, Menno P.J., additional, Joosten, Leo A.B., additional, van Elsas, Andrea, additional, Fayad, Zahi A., additional, Rialdi, Alexander, additional, Torre, Denis, additional, Guccione, Ernesto, additional, Ochando, Jordi, additional, Netea, Mihai G., additional, Griffioen, Arjan W., additional, and Mulder, Willem J.M., additional

Published
2020
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30. The effect of BCG vaccination on alveolar macrophages obtained from induced sputum from healthy volunteers

Author

Koeken, Valerie A.C.M., primary, van der Pasch, Eva S., additional, Leijte, Guus P., additional, Mourits, Vera P., additional, de Bree, L. Charlotte J., additional, Moorlag, Simone J.C.F.M., additional, Budnick, Isadore, additional, Idh, Nina, additional, Lerm, Maria, additional, Kox, Matthijs, additional, van Laarhoven, Arjan, additional, Netea, Mihai G., additional, and van Crevel, Reinout, additional

Published
2020
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31. BCG-Induced Trained Immunity in Healthy Individuals: The Effect of Plasma Muramyl Dipeptide Concentrations

Author

Mourits, Vera P., primary, Koeken, Valerie A. C. M., additional, de Bree, L. Charlotte J., additional, Moorlag, Simone J. C. F. M., additional, Chu, Wern Cui, additional, Xu, Xiaoli, additional, Dijkstra, Helga, additional, Lemmers, Heidi, additional, Joosten, Leo A. B., additional, Wang, Yue, additional, van Crevel, Reinout, additional, and Netea, Mihai G., additional

Published
2020
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32. The Set7 Lysine Methyltransferase Regulates Plasticity in Oxidative Phosphorylation Necessary for Trained Immunity Induced by β-Glucan

Author

Keating, Samuel T., primary, Groh, Laszlo, additional, van der Heijden, Charlotte D.C.C., additional, Rodriguez, Hanah, additional, dos Santos, Jéssica C., additional, Fanucchi, Stephanie, additional, Okabe, Jun, additional, Kaipananickal, Harikrishnan, additional, van Puffelen, Jelmer H., additional, Helder, Leonie, additional, Noz, Marlies P., additional, Matzaraki, Vasiliki, additional, Li, Yang, additional, de Bree, L. Charlotte J., additional, Koeken, Valerie A.C.M., additional, Moorlag, Simone J.C.F.M., additional, Mourits, Vera P., additional, Domínguez-Andrés, Jorge, additional, Oosting, Marije, additional, Bulthuis, Elianne P., additional, Koopman, Werner J.H., additional, Mhlanga, Musa, additional, El-Osta, Assam, additional, Joosten, Leo A.B., additional, Netea, Mihai G., additional, and Riksen, Niels P., additional

Published
2020
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33. The role of Toll‐like receptor 10 in modulation of trained immunity

Author

Mourits, Vera P., primary, Arts, Rob J.W., additional, Novakovic, Boris, additional, Matzaraki, Vasiliki, additional, Bree, L. Charlotte J., additional, Koeken, Valerie A.C.M., additional, Moorlag, Simone J.C.F.M., additional, Puffelen, Jelmer H., additional, Groh, Laszlo, additional, Heijden, Charlotte D.C.C., additional, Keating, Sam T., additional, Netea, Mihai G., additional, Oosting, Marije, additional, and Joosten, Leo A.B., additional

Published
2019
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34. The role of Toll‐like receptor 10 in modulation of trained immunity.

Author

Mourits, Vera P., Arts, Rob J.W., Novakovic, Boris, Matzaraki, Vasiliki, Bree, L. Charlotte J., Koeken, Valerie A.C.M., Moorlag, Simone J.C.F.M., Puffelen, Jelmer H., Groh, Laszlo, Heijden, Charlotte D.C.C., Keating, Sam T., Netea, Mihai G., Oosting, Marije, and Joosten, Leo A.B.

Subjects
*TOLL-like receptors, *SINGLE nucleotide polymorphisms, *BCG vaccines, *GREEN'S functions, *IMMUNOLOGIC memory, *PSYCHONEUROIMMUNOLOGY
Abstract

Summary: Toll‐like receptor 10 (TLR10) is the only member of the human Toll‐like receptor family with an inhibitory function on the induction of innate immune responses and inflammation. However, its role in the modulation of trained immunity (innate immune memory) is unknown. In the present study, we assessed whether TLR10 modulates the induction of trained immunity induced by β‐glucan or bacillus Calmette–Guérin (BCG). Interleukin 10 receptor antagonist production was increased upon activation of TLR10 ex vivo after BCG vaccination, and TLR10 protein expression on monocytes was increased after BCG vaccination, whereas anti‐TLR10 antibodies did not significantly modulate β‐glucan or BCG‐induced trained immunity in vitro. A known immunomodulatory TLR10 missense single‐nucleotide polymorphism (rs11096957) influenced trained immunity responses by β‐glucan or BCG in vitro. However, the in vivo induction of trained immunity by BCG vaccination was not influenced by TLR10 polymorphisms. In conclusion, TLR10 has a limited, non‐essential impact on the induction of trained immunity in humans. [ABSTRACT FROM AUTHOR]

Published
2020
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35. A single-cell view on host immune transcriptional response to in vivoBCG-induced trained immunity

Author

Li, Wenchao, Moorlag, Simone J.C.F.M., Koeken, Valerie A.C.M., Röring, Rutger J., de Bree, L. Charlotte J., Mourits, Vera P., Gupta, Manoj K., Zhang, Bowen, Fu, Jianbo, Zhang, Zhenhua, Grondman, Inge, van Meijgaarden, Krista E., Zhou, Liang, Alaswad, Ahmed, Joosten, Leo A.B., van Crevel, Reinout, Xu, Cheng-Jian, Netea, Mihai G., and Li, Yang

Abstract

Bacillus Calmette-Guérin (BCG) vaccination is a prototype model for the study of trained immunity (TI) in humans, and results in a more effective response of innate immune cells upon stimulation with heterologous stimuli. Here, we investigate the heterogeneity of TI induction by single-cell RNA sequencing of immune cells collected from 156 samples. We observe that both monocytes and CD8+T cells show heterologous transcriptional responses to lipopolysaccharide, with an active crosstalk between these two cell types. Furthermore, the interferon-γ pathway is crucial in BCG-induced TI, and it is upregulated in functional high responders. Data-driven analyses and functional experiments reveal STAT1to be one of the important transcription factors for TI shared in all identified monocyte subpopulations. Finally, we report the role of type I interferon-related and neutrophil-related TI transcriptional programs in patients with sepsis. These findings provide comprehensive insights into the importance of monocyte heterogeneity during TI in humans.

Published
2023
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36. In vitroinduction of trained immunity in adherent human monocytes

Author

Domínguez-Andrés, Jorge, Arts, Rob J.W., Bekkering, Siroon, Bahrar, Harsh, Blok, Bastiaan A., de Bree, L. Charlotte J., Bruno, Mariolina, Bulut, Özlem, Debisarun, Priya A., Dijkstra, Helga, Cristina dos Santos, Jéssica, Ferreira, Anaísa V., Flores-Gomez, Daniela, Groh, Laszlo A., Grondman, Inge, Helder, Leonie, Jacobs, Cor, Jacobs, Liesbeth, Jansen, Trees, Kilic, Gizem, Klück, Viola, Koeken, Valerie A.C.M., Lemmers, Heidi, Moorlag, Simone J.C.F.M., Mourits, Vera P., van Puffelen, Jelmer H., Rabold, Katrin, Röring, Rutger J., Rosati, Diletta, Tercan, Helin, van Tuijl, Julia, Quintin, Jessica, van Crevel, Reinout, Riksen, Niels P., Joosten, Leo A.B., and Netea, Mihai G.

Abstract

A growing number of studies show that innate immune cells can undergo functional reprogramming, facilitating a faster and enhanced response to heterologous secondary stimuli. This concept has been termed “trained immunity.” We outline here a protocol to recapitulate this in vitrousing adherent monocytes from consecutive isolation of peripheral blood mononuclear cells. The induction of trained immunity and the associated functional reprogramming of monocytes is described in detail using β-glucan (from Candida albicans) and Bacillus Calmette-Guérin as examples.

Published
2021
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37. Additional file 5 of Integration of metabolomics, genomics, and immune phenotypes reveals the causal roles of metabolites in disease

Author

Chu, Xiaojing, Jaeger, Martin, Beumer, Joep, Bakker, Olivier B., Aguirre-Gamboa, Raul, Oosting, Marije, Smeekens, Sanne P., Moorlag, Simone, Mourits, Vera P., Koeken, Valerie A. C. M., de Bree, Charlotte, Jansen, Trees, Mathews, Ian T., Dao, Khoi, Najhawan, Mahan, Watrous, Jeramie D., Joosten, Irma, Sharma, Sonia, Koenen, Hans J. P. M., Withoff, Sebo, Jonkers, Iris H., Netea-Maier, Romana T., Xavier, Ramnik J., Franke, Lude, Xu, Cheng-Jian, Joosten, Leo A. B., Sanna, Serena, Jain, Mohit, Kumar, Vinod, Clevers, Hans, Wijmenga, Cisca, Netea, Mihai G., and Li, Yang

Subjects
3. Good health
Abstract

Additional file 5. Fig. S1-8

38. Additional file 25 of Integration of metabolomics, genomics, and immune phenotypes reveals the causal roles of metabolites in disease

Author

Chu, Xiaojing, Jaeger, Martin, Beumer, Joep, Bakker, Olivier B., Aguirre-Gamboa, Raul, Oosting, Marije, Smeekens, Sanne P., Moorlag, Simone, Mourits, Vera P., Koeken, Valerie A. C. M., de Bree, Charlotte, Jansen, Trees, Mathews, Ian T., Dao, Khoi, Najhawan, Mahan, Watrous, Jeramie D., Joosten, Irma, Sharma, Sonia, Koenen, Hans J. P. M., Withoff, Sebo, Jonkers, Iris H., Netea-Maier, Romana T., Xavier, Ramnik J., Franke, Lude, Xu, Cheng-Jian, Joosten, Leo A. B., Sanna, Serena, Jain, Mohit, Kumar, Vinod, Clevers, Hans, Wijmenga, Cisca, Netea, Mihai G., and Li, Yang

Subjects
3. Good health
Abstract

Additional file 25. Review history.

39. Additional file 5 of Integration of metabolomics, genomics, and immune phenotypes reveals the causal roles of metabolites in disease

Author

Chu, Xiaojing, Jaeger, Martin, Beumer, Joep, Bakker, Olivier B., Aguirre-Gamboa, Raul, Oosting, Marije, Smeekens, Sanne P., Moorlag, Simone, Mourits, Vera P., Koeken, Valerie A. C. M., de Bree, Charlotte, Jansen, Trees, Mathews, Ian T., Dao, Khoi, Najhawan, Mahan, Watrous, Jeramie D., Joosten, Irma, Sharma, Sonia, Koenen, Hans J. P. M., Withoff, Sebo, Jonkers, Iris H., Netea-Maier, Romana T., Xavier, Ramnik J., Franke, Lude, Xu, Cheng-Jian, Joosten, Leo A. B., Sanna, Serena, Jain, Mohit, Kumar, Vinod, Clevers, Hans, Wijmenga, Cisca, Netea, Mihai G., and Li, Yang

Subjects
3. Good health
Abstract

Additional file 5. Fig. S1-8

40. Additional file 25 of Integration of metabolomics, genomics, and immune phenotypes reveals the causal roles of metabolites in disease

Author

Chu, Xiaojing, Jaeger, Martin, Beumer, Joep, Bakker, Olivier B., Aguirre-Gamboa, Raul, Oosting, Marije, Smeekens, Sanne P., Moorlag, Simone, Mourits, Vera P., Koeken, Valerie A. C. M., de Bree, Charlotte, Jansen, Trees, Mathews, Ian T., Dao, Khoi, Najhawan, Mahan, Watrous, Jeramie D., Joosten, Irma, Sharma, Sonia, Koenen, Hans J. P. M., Withoff, Sebo, Jonkers, Iris H., Netea-Maier, Romana T., Xavier, Ramnik J., Franke, Lude, Xu, Cheng-Jian, Joosten, Leo A. B., Sanna, Serena, Jain, Mohit, Kumar, Vinod, Clevers, Hans, Wijmenga, Cisca, Netea, Mihai G., and Li, Yang

Subjects
3. Good health
Abstract

Additional file 25. Review history.

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