Abstract
Tuberculosis is still a major health problem worldwide. Currently it is not known what kind of immune responses lead to successful control and clearance of Mycobacterium tuberculosis. This gap in knowledge is reflected by the inability to develop sufficient diagnostic and therapeutic tools to fight tuberculosis. We have used the Mycobacterium marinum infection model in the adult zebrafish and taken advantage of heterogeneity of zebrafish population to dissect the characteristics of adaptive immune responses, some of which are associated with well-controlled latency or bacterial clearance while others with progressive infection. Differences in T cell responses between subpopulations were measured at the transcriptional level. It was discovered that a high total T cell level was usually associated with lower bacterial loads alongside with a T helper 2 (Th2)-type gene expression signature. At late time points, spontaneous reactivation with apparent symptoms was characterized by a low Th2/Th1 marker ratio and a substantial induction of foxp3 reflecting the level of regulatory T cells. Characteristic gata3/tbx21 has potential as a biomarker for the status of mycobacterial disease.
Highlights
Tuberculosis (TB) is a pulmonary disease spread worldwide
Expansion of T lymphocytes is associated with limited mycobacterial growth in the zebrafish
To further demonstrate the significance of lymphocyte responses in the immune defence against mycobacteria in zebrafish, we carried out adoptive transfer experiments on low-dose (2167 cfu) M. marinum-infected rag1 (2/2) fish
Summary
Tuberculosis (TB) is a pulmonary disease spread worldwide It is caused by an infection with Mycobacterium tuberculosis. 5–10% of infected individuals develop a primary active disease while the most common outcome of infection is a latent or subclinical disease with no evident symptoms. This latent disease has the inherent ability to reactivate after years or even decades of latency and is a major global threat. The dichotomy to a latent and active tuberculosis is an oversimplification, as the infection can lead to a wide spectrum of disease states ranging from a well-controlled (or even cleared) latent disease to fulminant, severe forms of TB. Observations of an early Th1 response (2–3 weeks post infection, wpi) followed by a Th2 response simultaneously with the onset of a chronic phase, have led to a presumption that Th2 response is detrimental to the host by leading to a failure of Th1 response to clear the
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