Alterações da expressão da proteína PHEX na Hanseníase

Abstract

Leprosy is an infectious disease caused by Mycobacterium leprae, an obligate intracellular bacillus that proliferates at lower temperature-body locals, particularly skin and peripheral nerves, within cells such as macrophages and Schwann cells. It is transmitted by mucosae from airways, probably by aerosol from infected individuals. Human beings are the natural hosts, and bacilli are slowly multiplied, with a 14-day estimate of generation period. In spite of the minimum variation of M. leprae genoma, the disease is characterized by a well-defined spectrum of clinical forms, resulting from host immune response ability. Among multibacillary patients (MB), the disease is disseminated, with a number of skin lesions and a considerable bacillary proliferation. These individuals present cellular hyporresponsiveness to M. leprae. Paucibacillary patients (PB) show either one or a few lesions, the bacillary load is insignificant, being sometimes unlikely to be observed by traditional bacilloscopy, and there occurs a pathogen-specific immune response. The physical disabilities often observed among these patients result from neuropathies and osteopathy, and may be irreversible.Such deformities may progress even after the bacillary load reduction upon completion of multidrug therapy (MDT).This thesis aimed at the study of implications of PHEX protein in leprosy physiopathologic alterations, and particularly in bone alterations. PHEX (Phosphate-regulating gene with Homologies to Endopeptidase on the X chromosome) is expressed in several human cells and, at the first paper encompassed by this thesis, we demonstrated that M. leprae leads to the reduction of PHEX expression in lineages of Schwann cells and human osteoblasts. Such effect was also caused by mycobacteria of other species. At the second manuscript already submitted and under review, we noted that, in blood leukocytes of leprosy patients, there was also a negative modulation of PHEX, and that this effect was neither related to the production of M. leprae-specific inflammatory cytokines in vitro nor to the appearance of biochemical alterations. Therefore, our results suggest that the negative modulation of PHEX may contribute to leprosy bone disease. It appear as a characteristic feature of other mycobacteriosis, and may help to justify their ability to survive and penetrate the bone.