Abstract
BackgroundMycobacterium tuberculosis infection is known to cause inflammation and lung tissue damage in high-risk populations. Nevertheless, direct associations between mycobacterial loads, systemic inflammation and pulmonary lesions upon treatment initiation have not been fully characterized. In the present exploratory study, we prospectively depict the immune profile, microbial clearance and evolution of radiographic lesions in a pulmonary tuberculosis (PTB) patient cohort before and 60 days after anti-tuberculous treatment (ATT) initiation.MethodsCirculating levels of cytokines (IL-2, IL-4, IL-6, IL-10, IFN-γ, TNF-α) and C-reactive protein (CRP), as well as values of erythrocyte sedimentation rate (ESR) were measured in cryopreserved serum samples obtained from 73 PTB patients at pre-ATT and day 60 of treatment. Changes of the immune profile over time were compared with mycobacterial loads in sputum and culture conversion at day 60 of ATT. Additional analyses tested associations between improvement of chest radiographic lesions at day 60 and pre-treatment status of inflammation and mycobacterial loads.ResultsWithin the inflammatory parameters evaluated, values of CRP, IL-2, IL-4, TNF-α and ESR significantly decreased upon treatment initiation. On the converse, IL-10 levels substantially increased at day 60 of ATT, whereas concentrations of IL-6 and IFN-γ remained unchanged. Multidimensional analyses revealed that ESR, IL-2, IL-4 and CRP were the parameters with the highest power to discriminate individuals before and after treatment initiation. We further demonstrated that higher bacterial loads in sputum at pre-ATT were associated with increased systemic inflammation and higher risk for positive M. tuberculosis sputum cultures at day 60 of treatment. Furthermore, we found that pre-ATT mycobacterial loads in sputum and systemic inflammation synergistically associated with the status of radiographic lesions during treatment (Relative risk for chest X-ray improvement: 10.0, 95 % confidence interval: 2.4–40.0, P = 0.002).ConclusionsM. tuberculosis loads in sputum are directly associated to the status of systemic inflammation and potentially impact the immune profile, culture conversion and evolution of lung lesions upon ATT initiation.Electronic supplementary materialThe online version of this article (doi:10.1186/s12879-016-1736-3) contains supplementary material, which is available to authorized users.
Highlights
Mycobacterium tuberculosis infection is known to cause inflammation and lung tissue damage in high-risk populations
Multidimensional analyses revealed that erythrocyte sedimentation rate (ESR), IL-2, IL-4 and C-reactive protein (CRP) were the parameters with the highest power to discriminate individuals before and after treatment initiation
We further demonstrated that higher bacterial loads in sputum at pre-anti-tuberculous treatment (ATT) were associated with increased systemic inflammation and higher risk for positive M. tuberculosis sputum cultures at day 60 of treatment
Summary
Mycobacterium tuberculosis infection is known to cause inflammation and lung tissue damage in high-risk populations. In the present exploratory study, we prospectively depict the immune profile, microbial clearance and evolution of radiographic lesions in a pulmonary tuberculosis (PTB) patient cohort before and 60 days after anti-tuberculous treatment (ATT) initiation. Only 10 % of individuals exposed to M. tuberculosis develop active disease, which highlights the importance of understanding the key determinants of susceptibility to infection. The determinants of the TB clinical presentation are described to involve a complex relationship between the mycobacterium and the host immune responses [2, 3]. Successful host response against M. tuberculosis requires the production of proinflammatory cytokines including IFN-γ and TNF-α [4, 5]. Individuals genetically deficient in molecules from the IFN pathway, as well as those under treatment of chronic conditions with TNF-α blockers, are highly susceptible to severe TB [6]. Host biomarkers for monitoring treatment response have been considered as important priorities for TB research [8]
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