Cytokine/chemokine profiles in people with recent infection by Mycobacterium tuberculosis

Abstract

Introduction: The risk of progression to tuberculosis disease is highest within the first year after M. tuberculosis infection (TBI). We hypothesize that people with newly acquired TBI have a unique cytokine/chemokine profile that could be used as a potential biomarker.

Methods: We evaluated socio-demographic variables and 18 cytokines/chemokines in plasma samples from a cohort of people deprived of liberty (PDL) in two Colombian prisons: 47 people diagnosed with pulmonary TB, 24 with new TBI, and 47 non-infected individuals. We performed a multinomial regression to identify the immune parameters that differentiate the groups.

Results: The concentration of immune parameters changed over time and was affected by the time of incarceration. The concentration of sCD14, IL-18 and IP-10 differed between individuals with new TBI and short and long times of incarceration. Among people with short incarceration, high concentrations of MIP-3α were associated with a higher risk of a new TBI, and higher concentrations of Eotaxin were associated with a lower risk of a new TBI. Higher concentrations of sCD14 and TNF-α were associated with a higher risk of TB disease, and higher concentrations of IL-18 and MCP-1 were associated with a lower risk of TB disease.

Conclusions: There were cytokines/chemokines associated with new TBI and TB disease. However, the concentration of immune mediators varies by the time of incarceration among people with new TBI. Further studies should evaluate the changes of these and other cytokines/chemokines over time to understand the immune mechanisms across the spectrum of TB.

Keywords: Mycobacterium tuberculosis; TST conversion; chemokines; cytokines; tuberculosis; tuberculosis infection.

Figure 1

Flow chart of people included in the study. TB: tuberculosis; TST: tuberculin skin test. New TBI [people with negative two-step TST that became positive during follow-up were divided into TBI with short incarceration (they had ≤3 months of incarceration at enrolment) and TBI with long incarceration (they had ≥1 year of incarceration at enrolment)].

Figure 2

Cytokines/chemokines concentrations among people with new latent tuberculosis infection at baseline, pre-conversion, and TST conversion, by the time of incarceration. New TBI [people with negative two-step TST that became positive during follow-up were divided into new TBI with short incarceration (they had ≤3 months of incarceration at enrolment) and new TBI with long incarceration (they had ≥1 year of incarceration at enrolment)]. Values are reported in pg/ml for all cytokines/chemokines, except for sCD14 where results are reported in ng/ml. Boxplots are median and interquartile range. (A) MIP-3α; (B) Eotaxin; (C) sCD14; (ng/ml) (D) INF-γ; (E) IL-18; (F) MIP-1β; (G) MCP-1; (H) IP-10; (I) TNF-α.

Figure 3

Immune parameters concentrations among people who converted the TST (new TBI with short incarceration [n= 11] and TBI with long incarceration [n= 13]), people diagnosed with TB disease (n=47), and non-infected people (n=47). New TBI [people with negative two-step TST that became positive during follow-up were divided into new TBI with short incarceration (they had ≤3 months of incarceration at enrolment) and new TBI with long incarceration (they had ≥1 year of incarceration at enrolment)]. (A) MIP-3α; (B) Eotaxin; (C) sCD14 (ng/ml); (D) INF-γ; (E) IL-18; (F) MIP-1β; (G) MCP-1; (H) IP-10; (I) TNF-α. Values reported in pg/ml for all cytokines, except for sCD14 reported in ng/ml. Boxplots are median and interquartile range. p-value using the Mann-Whitney U test and adjusted by multiple comparisons.