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Citations to this article

Mycobacterial growth inhibition is associated with trained innate immunity
Simone A. Joosten, … , Mihai G. Netea, Tom H.M. Ottenhoff
Simone A. Joosten, … , Mihai G. Netea, Tom H.M. Ottenhoff
Published February 20, 2018
Citation Information: J Clin Invest. 2018;128(5):1837-1851. https://doi.org/10.1172/JCI97508.
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Research Article Immunology Infectious disease Article has an altmetric score of 3

Mycobacterial growth inhibition is associated with trained innate immunity

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Abstract

The lack of defined correlates of protection hampers development of vaccines against tuberculosis (TB). In vitro mycobacterial outgrowth assays are thought to better capture the complexity of the human host/Mycobacterium tuberculosis (Mtb) interaction. Here, we used a mycobacterial growth inhibition assay (MGIA) based on peripheral blood mononuclear cells to investigate the capacity to control outgrowth of bacille Calmette-Guérin (BCG). Interestingly, strong control of BCG outgrowth was observed almost exclusively in individuals with recent exposure to Mtb, but not in (long-term) latent TB infection, and only modestly in BCG vaccinees. Mechanistically, control of mycobacterial outgrowth strongly correlated with the presence of a CD14dim monocyte population, but also required the presence of T cells. The nonclassical monocytes produced CXCL10, and CXCR3 receptor blockade inhibited the capacity to control BCG outgrowth. Expression of CXCR3 splice variants was altered in recently Mtb-exposed individuals. Cytokines previously associated with trained immunity were detected in MGIA supernatants, and CXCL9, CXCL10, and CXCL11 represent new markers of trained immunity. These data indicate that CXCR3 ligands are associated with trained immunity and are critical factors in controlling mycobacterial outgrowth. In conclusion, control of mycobacterial outgrowth early after exposure to Mtb is the result of trained immunity mediated by a CXCL10-producing nonclassical CD14dim monocyte subset.

Authors

Simone A. Joosten, Krista E. van Meijgaarden, Sandra M. Arend, Corine Prins, Fredrik Oftung, Gro Ellen Korsvold, Sandra V. Kik, Rob J.W. Arts, Reinout van Crevel, Mihai G. Netea, Tom H.M. Ottenhoff

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Expert Review of Vaccines 2019
RUTI Vaccination Enhances Inhibition of Mycobacterial Growth ex vivo and Induces a Shift of Monocyte Phenotype in Mice
SA Prabowo, H Painter, A Zelmer, SG Smith, K Seifert, M Amat, PJ Cardona, HA Fletcher
Frontiers in immunology 2019
In vitro Mycobacterial Growth Inhibition in South Korean Adults With Latent TB Infection
H Lee, J Kim, YA Kang, DR Kim, B Sim, A Zelmer, HA Fletcher, HM Dockrell, SG Smith, SN Cho
Frontiers in immunology 2019
Induction of memory-like dendritic cell responses in vivo
CR Hole, CM Wager, N Castro-Lopez, A Campuzano, H Cai, KL Wozniak, Y Wang, FL Wormley
Nature Communications 2019
Disparate Tuberculosis Disease Development in Macaque Species Is Associated With Innate Immunity
K Dijkman, RA Vervenne, CC Sombroek, C Boot, SO Hofman, KE van Meijgaarden, TH Ottenhoff, CH Kocken, KG Haanstra, MP Vierboom, FA Verreck
Frontiers in immunology 2019
BCG-Induced Cross-Protection and Development of Trained Immunity: Implication for Vaccine Design
C Covián, A Fernández-Fierro, A Retamal-Díaz, FE Díaz, AE Vasquez, MK Lay, CA Riedel, PA González, SM Bueno, AM Kalergis
Frontiers in immunology 2019
Whole blood RNA signatures in leprosy patients identify reversal reactions before clinical onset: a prospective, multicenter study
M Tió-Coma, A van Hooij, K Bobosha, JJ van der Ploeg-van Schip, S Banu, S Khadge, P Thapa, CB Kunwar, IM Goulart, Y Bekele, DA Hagge, MO Moraes, RM Teles, RO Pinheiro, EW van Zwet, JJ Goeman, A Aseffa, MC Haks, TH Ottenhoff, RL Modlin, A Geluk
Scientific Reports 2019
Optimisation, harmonisation and standardisation of the direct mycobacterial growth inhibition assay using cryopreserved human peripheral blood mononuclear cells
R Tanner, SG Smith, KE van Meijgaarden, F Giannoni, M Wilkie, L Gabriele, C Palma, HM Dockrell, TH Ottenhoff, H McShane
Journal of Immunological Methods 2019
Hypoxia-inducible factor-1α regulation of myeloid cells
CL Stothers, L Luan, BA Fensterheim, JK Bohannon
Journal of Molecular Medicine 2018
Friends and foes of tuberculosis: modulation of protective immunity
S Brighenti, SA Joosten
Journal of Internal Medicine 2018
Mycobacterium Growth Inhibition Assay of Human Alveolar Macrophages as a Correlate of Immune Protection Following Mycobacterium bovis Bacille Calmette–Guérin Vaccination
J Radloff, J Heyckendorf, L van der Merwe, PS Carballo, N Reiling, E Richter, C Lange, B Kalsdorf
Frontiers in immunology 2018

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