Abstract
BackgroundCD69 is a biomarker of T-cell activation status, but its activation status in human Mycobacterium tuberculosis (Mtb) infection remains elusive.MethodsA set of cohorts of patients with different tuberculosis (TB) infection status including active TB patients (ATB), latent tuberculous infection patients (LTBI) and close contacts (CCs) of ATB was designed, and the expression profiles of CD69 and several T-cell markers were determined on Mtb antigen-stimulated T cells by flow cytometry.ResultsThe frequencies of CD4+ and CD8+ T cells were both comparable among Mtb-infected individuals including ATB and LTBI, which guaranteed the consistency of the background level. A t-Distributed Stochastic Neighbor Embedding (tSNE) analysis on a panel of six phenotypic markers showed a unique color map axis gated on T cells in the CCs group compared with ATB and LTBI populations. By further gating on cells positive for each individual marker and then overlaying those events on top of the tSNE plots, their distribution suggested that some markers were expressed differently in the CCs group. Further analysis showed that the expression levels of CD69 on both CD4+ and CD8+ T cells were significantly lower in the CCs group, especially in interferon-γ-responding T cells.ConclusionOur findings suggest that the T-cell activation status of CD69 is associated with Mtb infection and may have the potential to distinguish LTBI from those populations who have been exposed continuously to Mtb but have not become infected.
Highlights
Tuberculosis (TB) is the leading cause of death due to a single infectious disease in the world, there were an estimated 10 million new TB cases and 1.5 million deaths in the year of 2018 (WHO, 2019)
To explore the role of T cells in close contacts of TB patients, we firstly compared the frequencies of CD4+ and CD8+ T cells among TB, latent TB infection (LTBI) and CCs groups
These data suggest that the activation status of CD69 is associated with Mycobacterium tuberculosis (Mtb) infection and may have the potential to distinguish LTBI from those populations who are exposed continuously to Mtb but are not infected
Summary
Tuberculosis (TB) is the leading cause of death due to a single infectious disease in the world, there were an estimated 10 million new TB cases and 1.5 million deaths in the year of 2018 (WHO, 2019). It was reported that nine months of isoniazid or four months of rifampin treatment can prevent the development of active TB disease in persons with LTBI (Samanovic and Darwin, 2016), illustrating the feasibility of sterile eradiation of Mtb in latent infection. Particular attention has been placed on the group of CCs with persistently negative TST/IGRA results despite prolonged exposure, a group termed “resisters” (Simmons et al, 2018; Kaipilyawar and Salgame, 2019). Identification of differential epidemiological and immunological characteristics of the CCs that are either “resisters” or LTBI will provide greater biological insights to prevent or clear early TB infections and develop novel diagnostic methods. CD69 is a biomarker of T-cell activation status, but its activation status in human Mycobacterium tuberculosis (Mtb) infection remains elusive
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