Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0026918 (Mycobacterium)
 52,428 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This study describes the changes occurring in vitro in nerve growth factor (NGF) production and expression of p75 by murine Schwann cells and neurofibroblasts, following infection with Mycobacterium leprae and in the presence of macrophage secretory products, using a semiquantitative ELISA. These parameters are compared in two strains of mice, Swiss White (SW) and C57B1/6, as they differ in their response to M. leprae infection; C57B1/6 is the 'resistant' strain. On infection, NGF levels remained unaltered in Schwann cells from both strains, while fibroblasts from C57B1/6 strain showed an increase in NGF production. Expression of p75 by Schwann cells was decreased on infection in both strains of mice. In vivo, this opposing effect of infection on NGF production and p75 expression by Schwann cells and neurofibroblasts may result in suboptimal amounts of NGF reaching neurons of the affected leprous nerves. Macrophage secretory products suppressed the production of NGF by infected neurofibroblasts from SW strain mice and the expression of p75 in Schwann cells from both strains. These results indicate that macrophages do not assist in nerve repair in leprosy and the differences in response to macrophage secretory products in the two strains suggests that different mechanisms of nerve repair operate in SW and C57B1/6 mice and presumably in lepromatous and tuberculoid patients.
 ...
PMID:Nerve growth factor production and expression of p75 by Schwann cells and neurofibroblasts in response to M. leprae infection and macrophage secretory products. 906 91

To investigate the role of cell-mediated immunity in the control of Mycobacterium avium infection, we studied the effects of targeted gene disruptions in components of the T lymphocyte-dependent, macrophage-mediated response on resistance of mice to this pathogen. Normal mice developed a chronic, asymptomatic infection, with rapid induction of mRNAs for IFN-gamma, IL-12, and TNF-alpha in spleen, liver, and lung. Bacterial loads in gene knockout, scid, and wild-type mice were indistinguishable for the first 4 wk of infection. However, by 8 wk postinfection, scid mice as well as animals with a targeted disruption of the IFN-gamma gene showed enhanced bacterial growth compared with wild-type controls. In contrast, knockout mice lacking the genes for the TNF-alpha p55/p75 receptors or inducible nitric oxide synthase not only developed comparable bacterial loads to wild-type animals, they also failed to display the splenomegaly and profound suppression of mitogen-induced lymphocyte proliferative responses evident in infected wild-type controls. Thus, M. avium is clearly distinct from other intracellular pathogens (e.g., Leishmania monocytogenes, Toxoplasma gondii, and Mycobacterium tuberculosis) whose initial replication in the host is tightly controlled by Th1-dependent effector mechanisms. Instead, the major effect of host cell-mediated immunity is to limit bacterial growth during the chronic phase of infection. Surprisingly, inducible nitric oxide appears to be more important for the immunopathology than for the host resistance induced by this bacterial pathogen.
 ...
PMID:Defects in cell-mediated immunity affect chronic, but not innate, resistance of mice to Mycobacterium avium infection. 914 97

This review examines the differences in the incidence, spectrum, and mechanisms of activation of opportunistic infections, such as Mycobacterium tuberculosis, in patients with rheumatic diseases treated with the soluble TNF p75 receptor etanercept compared to the 2 anti-TNF-alpha monoclonal antibodies, infliximab and adalimumab.
 ...
PMID:Differences between anti-tumor necrosis factor-alpha monoclonal antibodies and soluble TNF receptors in host defense impairment. 1574 64

Infection by virulent Mycobacterium avium caused progressive severe lymphopenia in C57BL/6 mice due to increased apoptosis rates. T-cell depletion did not occur in gamma interferon (IFN-gamma)-deficient mice which showed increased T-cell numbers and proliferation; in contrast, deficiency in nitric oxide synthase 2 did not prevent T-cell loss. Although T-cell loss was IFN-gamma dependent, expression of the IFN-gamma receptor on T cells was not required for depletion. Similarly, while T-cell loss was optimal if the T cells expressed IFN-gamma, CD8(+) T-cell depletion could occur in the absence of T-cell-derived IFN-gamma. Depletion did not require that the T cells be specific for mycobacterial antigen and was not affected by deficiencies in the tumor necrosis factor receptors p55 or p75, the Fas receptor (CD95), or the respiratory burst enzymes or by forced expression of bcl-2 in hematopoietic cells.
 ...
PMID:Gamma interferon-induced T-cell loss in virulent Mycobacterium avium infection. 1590 87

Tumor necrosis factor (TNF) is a critical component of both the antibacterially protective and the inflammatory responses against infections, particularly infections with intracellularly viable microorganisms. It is, therefore, not surprising that some treatment regimens that target TNF function have resulted in an increase in complications associated with infections due to such pathogens as Mycobacterium tuberculosis, Listeria monocytogenes, and Histoplasma capsulatum; organized granuloma formation is required to keep such infections under control. However, treatment with anti-TNF monoclonal antibodies (i.e., infliximab) has been associated with a higher incidence of granulomatous infections than has treatment with a TNF receptor (TNFR) p75 immunoglobulin G-fusion construct (i.e., etanercept). Three hypotheses concerning the mode of action of these 2 agents that might explain this difference are discussed here: differential induction of apoptosis or lysis in membrane TNF-expressing macrophages and T cells, differential inhibition of signaling via TNFRp55 and TNFRp75, and different net neutralizing capacities resulting from different pharmacologic properties.
 ...
PMID:Tumor necrosis factor and its blockade in granulomatous infections: differential modes of action of infliximab and etanercept? 1598

Leprosy is a chronic infectious disease that is caused by the obligate intracellular pathogen Mycobacterium leprae (M.leprae), which is the leading cause of all non-traumatic peripheral neuropathies worldwide. Although both myelinating and non-myelinating Schwann cells are infected by M.leprae in patients with lepromatous leprosy, M.leprae preferentially invades the non-myelinating Schwann cells. However, the effect of M.leprae infection on non-myelinating Schwann cells has not been elucidated. Lipid droplets (LDs) are found in M.leprae-infected Schwann cells in the nerve biopsies of lepromatous leprosy patients. M.leprae-induced LD formation favors intracellular M.leprae survival in primary Schwann cells and in a myelinating Schwann cell line referred to as ST88-14. In the current study, we initially characterized SW-10 cells and investigated the effects of LDs on M.leprae-infected SW-10 cells, which are non-myelinating Schwann cells. SW-10 cells express S100, a marker for cells from the neural crest, and NGFR p75, a marker for immature or non-myelinating Schwann cells. SW-10 cells, however, do not express myelin basic protein (MBP), a marker for myelinating Schwann cells, and myelin protein zero (MPZ), a marker for precursor, immature, or myelinating Schwann cells, all of which suggests that SW-10 cells are non-myelinating Schwann cells. In addition, SW-10 cells have phagocytic activity and can be infected with M. leprae. Infection with M. leprae induces the formation of LDs. Furthermore, inhibiting the formation of M. leprae-induced LD enhances the maturation of phagosomes containing live M.leprae and decreases the ATP content in the M. leprae found in SW-10 cells. These facts suggest that LD formation by M. leprae favors intracellular M. leprae survival in SW-10 cells, which leads to the logical conclusion that M.leprae-infected SW-10 cells can be a new model for investigating the interaction of M.leprae with non-myelinating Schwann cells.
 ...
PMID:The formation of lipid droplets favors intracellular Mycobacterium leprae survival in SW-10, non-myelinating Schwann cells. 2863 50