Abstract
BackgroundTuberculosis (TB) is associated with oxidative stress and the induction of host anti-oxidants to counteract this response. Heme oxygenase-1 (HO-1) is a critical promoter of cytoprotection in diverse disease models including mycobacterial infection. Nevertheless, the pattern of expression of HO-1 in human tuberculosis has not been studied. Here, we examine expression of HO-1 in M. tuberculosis-exposed and -infected individuals and test its ability to distinguish active from latent and successfully treated TB cases. In addition, we assess correlations between plasma levels of HO-1 and cytokines closely associated with the immunopathogenesis of TB.MethodsCross-sectional and longitudinal analyses of levels of HO-1, acute phase proteins and pro-inflammatory cytokines were performed in plasma samples from individuals with active pulmonary, extra-pulmonary or latent TB infection and healthy controls as part of a prospective cohort study in South India.ResultsSystemic levels of HO-1 were dramatically increased in individuals with active pulmonary and extra-pulmonary tuberculosis and particularly those with bilateral lung lesions and elevated bacillary loads in sputum. HO-1 levels effectively discriminated active from latent tuberculosis with higher predictive values than either C-reactive protein or serum amyloid protein. Moreover, there was a marked reduction in HO-1 levels in active TB cases following anti-tuberculous therapy but not in those who failed treatment. Pulmonary TB patients displaying the highest concentrations of HO-1 in plasma exhibited significantly elevated plasma levels of interleukin (IL)-10, interferon (IFN)-γ and IL-17 and diminished levels of tumor necrosis factor (TNF)-α.ConclusionThese findings establish HO-1 levels as a potentially useful parameter for distinguishing active from latent or treated pulmonary tuberculosis, that is superior in this respect to the measurement of other acute inflammatory proteins.
Highlights
The diagnosis of tuberculosis (TB) is a complex and lengthy process that involves the integration of clinical, radiological and microbiological parameters
The most widely used technique for confirming the presence of TB is the microscopic detection of acidfast bacilli (AFB) in sputum, that has a sensitivity ranging between 34–80% [1]
The tuberculin skin test (TST) and interferon-gamma (IFN-c) release assays, while useful for identifying individuals exposed to Mycobacterium tuberculosis, in themselves cannot be used for accurately establishing a diagnosis of active TB [3]; typically the diagnosis requires identification and/or culture of bacilli in biological fluids or tissue biopsies
Summary
The diagnosis of tuberculosis (TB) is a complex and lengthy process that involves the integration of clinical, radiological and microbiological parameters. Sputum cultures (both solid and liquid) are more sensitive and accurate than sputum smears, they are time consuming and often difficult to implement in resource limited regions highly endemic for TB. Another major challenge in TB diagnosis is the ability to distinguish active from latent TB infection (LTBI) [2]. In this regard, the tuberculin skin test (TST) and interferon-gamma (IFN-c) release assays, while useful for identifying individuals exposed to Mycobacterium tuberculosis, in themselves cannot be used for accurately establishing a diagnosis of active TB [3]; typically the diagnosis requires identification and/or culture of bacilli in biological fluids or tissue biopsies. We assess correlations between plasma levels of HO-1 and cytokines closely associated with the immunopathogenesis of TB
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