Avaliação do perfil de reconstituição imunológica de indivíduos HIV/TB submetidos a tratamento para tuberculose e terapia antirretroviral altamente ativa (haart) incluindo efavirenz / Profile assessment of immune reconstitution in HIV individuals / tb undergoing treatment for tuberculosis and highly active antiretroviral therapy (haart) including efavirenz

Mycobacterium tuberculosis (Mtb) e o vírus da imunodeficiência humana (HIV-1) são dois patógenos intracelulares que manipulam o sistema imune para gerar infecções persistentes. Ambas as infecções causam imunossupressão e ativação imune e, com a introdução da terapia antirretroviral altamente ativa (HAART), eventos como a síndrome da reconstituição imune (IRIS) podem ocorrer.Este estudo teve como objetivo avaliar os mecanismos de reconstituição imunológica de indivíduos com tuberculose (TB) e aids, em resposta aos respectivos tratamentos, analisando as subpopulações de células T, bem como os marcadores de ativação imunológica, o perfil de citocinas anti e pró-inflamatórias e a resposta aos antígenos de Mtb durante seis meses após a introdução da HAART. Estes parâmetros foram também avaliados de acordo com o status de imunossupressão dos pacientes no início do tratamento (células TCD4+ <200 ou ≥200 céls/mm3) e pelo desenvolvimento ou não da IRIS.Os pacientes incluídos neste estudo apresentaram restauração imune, com ganho de células TCD4+, redução da carga viral e da ativação imune, após a introdução da HAART...

Mycobacterium tuberculosis (Mtb) and human immunodeficiency vírus (HIV)are two intracellular pathogens that manipulate the immune system in order to generate persistent infections. Both infections cause immunosuppression and immune activationand, under Highly Active Antiretroviral Therapy (HAART), events like immunere constitution syndrome (IRIS) may occur. The objective of this study was to evaluate the immune reconstitution mechanisms among individual with tuberculosis (TB) andaids, in response to treatment to both diseases, based on the analyses of the T cellsubsets, immune activation markers, anti and pro-inflammatory cytokine profiles andresponses to Mtb antigens along six months after the introduction of HAART. These parameters were also evaluated according to the patients immunosuppression status atbaseline (CD4+<200 or greater than or equal to 200 cells/mm3) and the development or not of IRIS.The patients included in this study presented immune restoration, with gain ofCD4+T cells and reduction of viral load and immune activation after introduction of HAART...

Schwann cells producing matrix metalloproteinases under Mycobacterium leprae stimulation may play a role in the outcome of leprous neuropathy.

Matrix metalloproteinases (MMPs) mediate demyelination and breakdown of the blood-nerve barrier in peripheral neuropathies. Matrix metalloproteinases and tissue inhibitor of metalloproteinase 1 gene expression and secretion were studied in cells of the human Schwann cell line ST88-14 stimulated with Mycobacterium leprae and tumor necrosis factor (TNF) and in nerve biopsies from patients with neural leprosy (n = 21) and nonleprous controls (n = 3). Mycobacterium leprae and TNF induced upregulation of MMP-2 and MMP-9 and increased secretion of these enzymes in cultured ST88-14 cells. The effects of TNF and M. leprae were synergistic, and anti-TNF antibody blockage partially inhibited this synergistic effect. Nerves with inflammatory infiltrates and fibrosis displayed higher TNF, MMP-2, and MMP-9 mRNA than controls. Leprous nerve biopsies with no inflammatory alterations also exhibited higher MMP-2 and MMP-9; tissue inhibitor of metalloproteinase 1 was significantly higher in biopsies with fibrosis and inflammation. Immunohistochemical double labeling of the nerves demonstrated that the MMPs were mainly expressed by macrophages and Schwann cells. The biopsies with endoneurial inflammatory infiltrates and epithelioid granulomas had the highest levels of MMP-2 and MMP-9 mRNA detected. Together, these results suggest that M. leprae and TNF may directly induce Schwann cells to upregulate and secrete MMPs regardless of the extent of inflammation in leprous neuropathy.

Morphological and functional characterizations of Schwann cells stimulated with Mycobacterium leprae.

Nerve damage, a characteristic of leprosy, is the cause of patient deformities and a consequence of Schwann cells (SC) infection by Mycobacterium leprae. Although function/dysfunction of SC in human diseases like leprosy is difficult to study, many in vitro models, including SC lines derived from rat and/or human Schwannomas, have been employed. ST88-14 is one of the cell lineages used by many researchers as a model for M. leprae/SC interaction. However, it is necessary to establish the values and limitations of the generated data on the effects of M. leprae in these SC. After evaluating the cell line phenotype in the present study, it is close to non-myelinating SC, making this lineage an ideal model for M. leprae/SC interaction. It was also observed that both M. leprae and PGL-1, a mycobacterial cell-wall component, induced low levels of apoptosis in ST88-14 by a mechanism independent of Bcl-2 family members.

Morphological and functional characterizations of Schwann cells stimulated with Mycobacterium leprae

Nerve damage, a characteristic of leprosy, is the cause of patient deformities and a consequence of Schwann cells (SC) infection by Mycobacterium leprae. Although function/dysfunction of SC in human diseases like leprosy is difficult to study, many in vitro models, including SC lines derived from rat and/or human Schwannomas, have been employed. ST88-14 is one of the cell lineages used by many researchers as a model for M. leprae/SC interaction. However, it is necessary to establish the values and limitations of the generated data on the effects of M. leprae in these SC. After evaluating the cell line phenotype in the present study, it is close to non-myelinating SC, making this lineage an ideal model for M. leprae/SC interaction. It was also observed that both M. leprae and PGL-1, a mycobacterial cell-wall component, induced low levels of apoptosis in ST88-14 by a mechanism independent of Bcl-2 family members.