Mycobacterial-specific secretion of cytokines and chemokines in healthcare workers with apparent resistance to infection with Mycobacterium tuberculosis

Frontiers in Immunology

Immunology

Patrick DMC. Katoto¹  Avuyonke Balfour²  Nomawethu Masina²  Abulele Bekiswa²  Muki Shehu Shey³  Charlotte Schutz³  Graeme Meintjes³  Katalin Andrea Wilkinson⁴  Deborah Anne Lewinsohn⁵  David Lewinsohn⁶  Rachel Dielle⁷  Rene Goliath⁷ 

[1] Cochrane South Africa, South African Medical Research Council, Cape Town, South Africa;Centre for General Medicine and Global Health, Department of Medicine, University of Cape Town, Cape Town, South Africa;Centre for Tropical Diseases and Global Health and Department of Internal Medicine , Catholic University of Bukavu, Bukavu, Democratic Republic of Congo;Department of Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa;Wellcome Centre for Infectious Disease Research in Africa (CIDRI-Africa), Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa;Department of Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa;Wellcome Centre for Infectious Disease Research in Africa (CIDRI-Africa), Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa;Institute of Infectious Disease and Molecular Medicine (IDM), Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa;Department of Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa;Wellcome Centre for Infectious Disease Research in Africa (CIDRI-Africa), Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa;Institute of Infectious Disease and Molecular Medicine (IDM), Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa;Tuberculosis Laboratory, The Francis Crick Institute, London, United Kingdom;Division of Infectious Diseases, Department of Paediatrics, Oregon Health and Science University, Portland, OR, United States;Division of Pulmonary and Critical Care Medicine, Department of Medicine, Oregon Health and Science University, Portland, OR, United States;Wellcome Centre for Infectious Disease Research in Africa (CIDRI-Africa), Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa;

关键词: latent TB infection (LTBI);    resister;    cytokines;    chemokines;    Mycobacterium tuberculosis;    antibodies;   

DOI  :  10.3389/fimmu.2023.1176615

 received in 2023-02-28, accepted in 2023-05-08,  发布年份 2023

来源: Frontiers

【 摘 要 】

BackgroundCurrently, diagnosis of latent TB infection (LTBI) is based on the secretion of IFN-γ in response to Mycobacterium tuberculosis (Mtb) antigens, the absence of which is regarded as no infection. Some individuals appear to resist Mtb infection despite sustained exposure (resisters). In this study, we aimed to assess cytokines, chemokines and antibodies that may be associated with resistance to Mtb infection. We hypothesized that there may be an alternative immune response to Mtb exposure in the absence of IFN-γ in resisters.MethodsWe enrolled HIV-uninfected healthcare workers who had worked in high TB-exposure environments for 5 years or longer. We screened them for LTBI using the tuberculin skin test and the QuantiFERON-TB Gold Plus assay. We performed multiplex Luminex to measure concentrations of T cell-associated cytokines and chemokines as well as total antibodies in plasma collected from unstimulated fresh whole blood and supernatants from QuantiFERON-TB Gold Plus tubes following incubation of whole blood for 16-24 hours with ESAT6/CFP10 peptides.ResultsSamples from 78 individuals were analyzed: 33 resisters (TST<10mm; IGRA<0.35 IU/mL), 33 with LTBI (TST≥10mm and IGRA≥0.35 IU/mL) and 12 discordant (TST=0mm; IGRA≥1.0 IU/mL). There were no differences in concentrations of cytokines and chemokines in plasma between the different groups. Resisters had significantly lower concentrations of IFN-γ, IL-2, TNF-α, MIP-1α, MIP-1β, ITAC, IL-13 and GM-CSF in supernatants compared with LTBI group. There were no significant differences in the concentrations in supernatants of IL-10, IL-1β, IL-17A, IL-21, IL-23, MIP-3α, IL-4, IL-5, IL-6, IL-7, IL-8, Fractalkine and IL-12p70 between the groups. We observed that resisters had similar concentrations of total antibodies (IgG1, IgG2, IgG3, IgG4, IgA, and IgM) in plasma and supernatants compared to the LTBI and discordant groups.ConclusionResistance to Mtb infection despite sustained exposure is associated with lower Mtb-specific secretion of Th1-associated cytokines and chemokines. However, resisters showed secreted concentrations after Mtb stimulation of total antibodies and cytokines/chemokines associated with innate and Th17 immune responses similar to those with Mtb infection. This suggests an ability to mount non-IFN-γ immune responses to Mtb in apparent resisters.

【 授权许可】

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Copyright © 2023 Shey, Balfour, Masina, Bekiswa, Schutz, Goliath, Dielle, Katoto, Wilkinson, Lewinsohn, Lewinsohn and Meintjes