Mycobacterial growth inhibition is associated with trained innate immunity
| Autor: | Mihai G. Netea, Rob J.W. Arts, Tom H. M. Ottenhoff, Krista E. van Meijgaarden, Gro Ellen Korsvold, Simone A. Joosten, Fredrik Oftung, Sandra V. Kik, Sandra M. Arend, Corine Prins, Reinout van Crevel |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Male Receptors CXCR3 Population lnfectious Diseases and Global Health Radboud Institute for Molecular Life Sciences [Radboudumc 4] chemical and pharmacologic phenomena Biology CXCR3 Peripheral blood mononuclear cell Mycobacterium tuberculosis 03 medical and health sciences 0302 clinical medicine All institutes and research themes of the Radboud University Medical Center Immunity Latent Tuberculosis medicine CXCL10 Humans education education.field_of_study Innate immune system Monocyte General Medicine biology.organism_classification Immunity Innate 3. Good health 030104 developmental biology medicine.anatomical_structure lnfectious Diseases and Global Health Radboud Institute for Health Sciences [Radboudumc 4] Immunology Host-Pathogen Interactions BCG Vaccine Leukocytes Mononuclear Female Chemokines CXC 030215 immunology Research Article |
| Zdroj: | Journal of Clinical Investigation, 128, 5, pp. 1837-1851 Journal of Clinical Investigation Journal of Clinical Investigation, 128(5), 1837-1851 Journal of Clinical Investigation, 128, 1837-1851 |
| ISSN: | 0021-9738 |
| Popis: | 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-Guerin (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. |
| Databáze: | OpenAIRE |
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