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Human IFN-γ immunity to mycobacteria is governed by both IL-12 and IL-23
- Source :
- Science Immunology, Science Immunology, 2018, 3 (30), pp.eaau6759. ⟨10.1126/sciimmunol.aau6759⟩, Science Immunology, American Association for the Advancement of Science, 2018, 3 (30), pp.eaau6759. ⟨10.1126/sciimmunol.aau6759⟩
- Publication Year :
- 2018
- Publisher :
- American Association for the Advancement of Science (AAAS), 2018.
-
Abstract
- International audience; Hundreds of patients with autosomal recessive, complete IL-12p40 or IL-12Rβ1 deficiency have been diagnosed over the last 20 years. They typically suffer from invasive mycobacteriosis and, occasionally, from mucocutaneous candidiasis. Susceptibility to these infections is thought to be due to impairments of IL-12-dependent IFN-γ immunity and IL-23-dependent IL-17A/IL-17F immunity, respectively. We report here patients with autosomal recessive, complete IL-12Rβ2 or IL-23R deficiency, lacking responses to IL-12 or IL-23 only, all of whom, unexpectedly, display mycobacteriosis without candidiasis. We show that αβ T, γδ T, B, NK, ILC1, and ILC2 cells from healthy donors preferentially produce IFN-γ in response to IL-12, whereas NKT cells and MAIT cells preferentially produce IFN-γ in response to IL-23. We also show that the development of IFN-γ-producing CD4 + T cells, including, in particular , mycobacterium-specific TH1* cells (CD45RA− CCR6+), is dependent on both IL-12 and IL-23. Last, we show that IL12RB1, IL12RB2, and IL23R have similar frequencies of deleterious variants in the general population. The comparative rarity of symptomatic patients with IL-12Rβ2 or IL-23R deficiency, relative to IL-12Rβ1 deficiency , is, therefore, due to lower clinical penetrance. There are fewer symptomatic IL-23R-and IL-12Rβ2-deficient than IL-12Rβ1-deficient patients, not because these genetic disorders are rarer, but because the isolated absence of IL-12 or IL-23 is, in part, compensated by the other cytokine for the production of IFN-γ, thereby providing some protection against mycobacteria. These experiments of nature show that human IL-12 and IL-23 are both required for optimal IFN-γ dependent immunity to mycobacteria, both individually and much more so cooperatively.
- Subjects :
- MESH: Interleukin-12
0301 basic medicine
MESH: Interferon-gamma
MESH: Pedigree
medicine.medical_treatment
Immunology
Population
Mycobacterium Infections, Nontuberculous
Biology
Interleukin-23
Article
Mycobacterium
Interferon-gamma
03 medical and health sciences
0302 clinical medicine
Immune system
Immunity
MESH: Mycobacterium
medicine
Humans
Interferon gamma
education
Interleukin 12 receptor, beta 1 subunit
MESH: Interleukin-23
education.field_of_study
MESH: Humans
General Medicine
MESH: Mycobacterium Infections, Nontuberculous
Natural killer T cell
Interleukin-12
Immunity, Innate
Pedigree
3. Good health
030104 developmental biology
Cytokine
[SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics
Interleukin 12
[SDV.IMM]Life Sciences [q-bio]/Immunology
MESH: Immunity, Innate
030215 immunology
medicine.drug
Subjects
Details
- ISSN :
- 24709468
- Volume :
- 3
- Database :
- OpenAIRE
- Journal :
- Science Immunology
- Accession number :
- edsair.doi.dedup.....12b2d54fb97a024a1be58ace641d7fed
- Full Text :
- https://doi.org/10.1126/sciimmunol.aau6759