T
he year 007 has marked the 15th anniversary of the discovery by R.Koch of M. tuberculosis. R. Koch was a convinced optimist. He believed that tu-berculosis would be controlled during the few decades following his discovery.
Unfortunately, M. tuberculosis coexists with mankind since more than 15.000 years and, in response to selective pres-sures, the tubercle bacilli has improved its ability to adapt to its environment (e.g. multi- and extensive drug resist-ance).
Many researches in the TB field focus on the development of new vaccines, new diagnostic tests and new treatments.
This work, carried out in the Laboratory of Vaccinology and Mucosal Immunity, supports the contention that HBHA is a major candidate for new IGRAs. Ad-vantages of IGRAs are numerous, and large-scale applications of IGRAs would constitute a major advance in the rapid diagnosis of LTBI. Their use for the di-agnosis of active TB is more question-able, although they may be adapted to the local compartments (e.g. BAL, CSF).
This work also constitutes a start point for a large-scale, prospective study with HBHA-IGRA, that will be conducted in the laboratory.
The low levels of IFN-γ secretion during active TB in human provided an oppor-tunity to better understand TB patho-genesis. The characterization of this low peripheral HBHA-specific IFN-γ secre-tion has led to the discovery that active TB is characterized by the (excessive) presence of Treg cells. These Treg cells express classical markers for Treg cells, such as CD5, FoxP, CTLA-4, GITR and low levels of CD17. The Treg cells were specific for M. tuberculosis and were
in-ducible in the presence of mycobacteria and TGF-ß1 in vitro. Thus, the ability to induce Treg cells may be regarded as a virulence trait of M. tuberculosis. As they suppress protective immune responses, Treg cells can modify the disease out-come and represent therefore potential target cells for future therapeutic ap-proaches.
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