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)

Human Vgamma9Vdelta2 T cells contribute to immunity against intracellular pathogens and recognize nonpeptidic antigens, such as the mycobacterial phosphoantigen TUBAg. HIV infection is associated with a polyclonal decrease of peripheral Vgamma9Vdelta2 T cells and we previously reported that the remaining cells show a proliferative anergy to stimulation with Mycobacterium tuberculosis in 60% of patients. Because of alterations in the Th1/Th2 cytokine balance reported in HIV infection, we analyzed, at the single-cell level, the influence of exogenous IL-4, IL-10, IL-12 and IL-15 on the response to mycobacterial phosphoantigens of gammadelta T cells from HIV-infected patients and healthy donors. We report that the strong gammadelta T cell response to TUBAg is characterized by the rapid and selective production of the Th1/proinflammatory cytokines IFN-gamma and TNF-alpha in responder HIV-infected donors. In addition, a positive regulation by IL-12 and IL-15 of the production of these cytokines by Vgamma9Vdelta2 T cells in response to nonpeptidic ligands was observed, whereas IL-4 and IL-10 had no effect. In contrast, Vgamma9Vdelta2 T cells from the anergic HIV-infected donors had lost the ability to produce Th1 cytokines and were not shifted towards a Th2 profile. Furthermore, neither IL-12 nor IL-15 could reverse this functional anergy. The consequences of these observations are discussed in the context of HIV pathogenesis.
 ...
PMID:Regulation by cytokines (IL-12, IL-15, IL-4 and IL-10) of the Vgamma9Vdelta2 T cell response to mycobacterial phosphoantigens in responder and anergic HIV-infected persons. 993 90

To determine whether the Th1 response in tuberculosis correlated with IL-12R expression, we measured expression of the IL-12R beta 1 and IL-12R beta 2 subunits, as well as IL-12R beta 2 mRNA expression in tuberculosis patients and healthy tuberculin reactors. In tuberculosis patients, IFN-gamma production by Mycobacterium tuberculosis-stimulated PBMC was reduced, the percentages of T cells expressing IL-12R beta 1 and IL-12R beta 2 were significantly decreased, and IL-12R beta 2 mRNA expression was also markedly reduced. In contrast, in pleural fluid and lymph nodes at the site of disease in tuberculosis patients, in which IFN-gamma production is enhanced, IL-12R beta 2 mRNA expression was also increased. In M. tuberculosis-stimulated peripheral blood T cells from tuberculosis patients, anti-IL-10 and anti-TGF-beta enhanced IL-12R beta 1 and IL-12R beta 2 expression, and IFN-gamma production. In M. tuberculosis-stimulated peripheral blood T cells from healthy tuberculin reactors, recombinant IL-10 and TGF-beta reduced IL-12R beta 1 and IL-12R beta 2 expression, as well as IFN-gamma production. In combination with prior studies showing increased production of TGF-beta by blood monocytes from tuberculosis patients, this suggests that increased TGF-beta production is the underlying abnormality that reduces IL-12R beta 1 and IL-12R beta 2 expression in tuberculosis. Our findings provide evidence that IL-12R expression correlates well with IFN-gamma production in human tuberculosis, and that expression of IL-12R beta 1 and IL-12R beta 2 may play a central role in mediating a protective Th1 response.
 ...
PMID:Expression of the IL-12 receptor beta 1 and beta 2 subunits in human tuberculosis. 997 27

The pathogenic mechanisms of immunosuppression leading to susceptibility of Mycobacterium tuberculosis (MT) infection in chronic myelocytic leukemia (CML) are not clear. To address this issue, we measured the proliferative response, variation of T cell subpopulations (CD4+, CD8+, TCR-V delta 2 and TCR-V beta 8 T cells) and the cytokine profile (IL-1 beta, IL-2, IL-4, IL-6, IL-10, TNF-alpha, IFN-gamma) after MT stimulation of peripheral blood mononuclear cells (PBMC) in a patient with concomitant CML and active pulmonary tuberculosis. The results were compared to four patients with active pulmonary tuberculosis and no other coexistent diseases. The immunologic response to phytohemagglutinin (PHA) was also evaluated. In contrast to controls, the CML PBMC failed to proliferate in response to MT antigens. Mycobacterium-reactive CD4+, V delta 2 and V beta 8 T cells did not expand after MT stimulation of the CML PBMC. In MT antigens-stimulated cultures from the CML patient, IL-2 was not produced and mild reduction of IL-1 beta and INF-gamma were observed. In contrast, IL-10 was markedly elevated in these cultures. Similarly, PHA-stimulated PBMC from the CML patient showed no expansion of CD4+ and CD8+. T cells. In these cell cultures, INF-gamma concentration in supernatants was decreased and IL-10 was significantly elevated. This study suggests that patients with CML may present a profound immunosuppression of essential cellular and molecular immune effectors, a scenario which might contribute to the development of active tuberculosis. These findings further support the need of establishing immunotherapeutic modalities with potential value for myeloproliferative disorders.
 ...
PMID:Abnormal immunological response to Mycobacterium tuberculosis antigens in a patient with chronic myelocytic leukemia and active tuberculosis. 1002 42

Macrophage inhibitory factor-A3 (MIF-A3) is a fraction derived from Mycobacterium avium serovar 2 (Mav2) that consists of a small amine containing compound (peptide), trehalose and two or three short chain fatty acids. MIF-A3 has been shown to inhibit candidacidal activity of murine thioglycolate-elicited peritoneal-derived macrophages and bovine peripheral blood monocytes, and scavenge reactive oxygen intermediates. In this study, MIF-A3 was evaluated for its effect on secretion of IL-1beta, IL-6, IL-10, TNFalpha and GM-CSF in C57BL/6 murine thioglycolate-elicited peritoneal-derived macrophages, with and without pre-incubation with affinity purified goat anti-MIF-A3 IgG, using ELISA cytokine kit analysis. Results of this study suggest that anti-MIF-A3 IgG does not enhance clearance of Mav2, alter phagocytosis or alter phagosome-lysosome interactions as determined by electron microscopy in Mav2 infected macrophages. MIF-A3 does induce secretion of IL-6, but does not induce secretion of TNFalpha, IL-1beta, and GM-CSF. TNFalpha has been previously shown to reduce growth, while IL-6 has been shown to enhance growth of M. avium. Since IL-6 appears to enhance growth of M. avium and MIF-A3 induces IL-6 secretion, MIF-A3 may be responsible for enhanced intracellular growth in M. avium infections and be a factor in the pathogenesis of M. avium infections.
 ...
PMID:Effects of macrophage inhibitory factor-A3 (MIF-A3) on cytokine secretion and phagolysosome fusion in murine macrophages. 1006 27

To determine whether the extent of spread of Mycobacterium tuberculosis strains in the community correlated with their capacity to replicate in human macrophages, intracellular growth rates of M. tuberculosis patient isolates were measured. Strain 210 caused disease in 43 patients in central Los Angeles, 3 "small-cluster" strains caused disease in 8-23 patients, and 5 "unique" strains each caused disease in only 1 patient who was positive by sputum acid-fast smear and spent substantial amounts of time at homeless shelters that were tuberculosis transmission sites. Strain 210 isolates grew significantly more rapidly than small-cluster and unique strains in macrophages. All strains elicited production of similar amounts of tumor necrosis factor-alpha, interleukin (IL)-6, IL-10, and IL-12 and were equally susceptible to reactive nitrogen intermediates. It was concluded that the extensive spread of an M. tuberculosis strain correlated with its capacity to replicate rapidly in human macrophages, which may be a marker of virulence.
 ...
PMID:Enhanced capacity of a widespread strain of Mycobacterium tuberculosis to grow in human macrophages. 1019 Dec 25

We assessed the roles of proinflammatory cytokines IFN-gamma and TNF-alpha, and immunoregulatory cytokines IL-10 and TGF-beta in the modulation of the anti-microbial activity of murine peritoneal macrophages against Mycobacterium avium-intracellulare complex (MAIC). First, both IFN-gamma and TNF-alpha significantly reduced the bacterial growth in macrophages, indicating that these cytokines participate in up-regulation of macrophage anti-MAIC function. Second, although MAIC-infected macrophages produced substantial amounts of IL-10 and TGF-beta, neutralization of endogenous IL-10 and TGF-beta with anti-IL-10 and anti-TGF-beta antibodies, respectively, did not affect the intracellular growth of MAIC in macrophages from mice with BcgS (MAIC-susceptible) or BcgI (MAIC-resistant) genotype, regardless of the virulence of test MAIC strains. The same result was also obtained for macrophages stimulated with IFN-gamma or TNF-alpha. Third, in MAIC-infected mice, the growth of organisms at the sites of infection (lungs and spleens) was not affected by administration of anti-IL-10 or anti-TGF-beta antibodies. These findings indicate that, in the case of mice, endogenous IL-10 and TGF-beta are essentially ineffective in down-regulating macrophage anti-MAIC functions not only in vitro but also in vivo.
 ...
PMID:The modulating effects of proinflammatory cytokines interferon-gamma (IFN-gamma) and tumour necrosis factor-alpha (TNF-alpha), and immunoregulating cytokines IL-10 and transforming growth factor-beta (TGF-beta), on anti-microbial activity of murine peritoneal macrophages against Mycobacterium avium-intracellulare complex. 1019 15

The Bcg/Nramp1 gene controls early resistance and susceptibility of macrophages to mycobacterial infections. We previously reported that Mycobacterium tuberculosis-infected (Mtb) B10R (Bcgr) and B10S (Bcgs) macrophages differentially produce nitric oxide (NO-), leading to macrophage apoptosis. Since TNF-alpha and IL-10 have opposite effects on many macrophage functions, we determined the number of cells producing TNF-alpha and IL-10 in Mtb-infected or purified protein derivative-stimulated B10R and B10S macrophages lines, and Nramp1+/+ and Nramp1-/- peritoneal macrophages and correlated them with Mtb-mediated apoptosis. Mtb infection and purified protein derivative treatment induced more TNF-alpha+Nramp1+/+ and B10R, and more IL-10+Nramp1-/- and B10S cells. Treatment with mannosylated lipoarabinomannan, which rescues macrophages from Mtb-induced apoptosis, augmented the number of IL-10 B10R+ cells. Anti-TNF-alpha inhibited apoptosis, diminished NO- production, p53, and caspase 1 activation and increased Bcl-2 expression. In contrast, anti-IL-10 increased caspase 1 activation, p53 expression, and apoptosis, although there was no increment in NO- production. Murine rTNF-alpha induced apoptosis in noninfected B10R and B10S macrophages that was reversed by murine rIL-10 in a dose-dependent manner with concomitant inhibition of NO- production and caspase 1 activation. NO- and caspase 1 seem to be independently activated in that aminoguanidine did not affect caspase 1 activation and the inhibitor of caspase 1, Tyr-Val-Ala-Asp-acylooxymethylketone, did not block NO- production; however, both treatments inhibited apoptosis. These results show that Mtb activates TNF-alpha- and IL-10-dependent opposite signals in the induction of macrophage apoptosis and suggest that the TNF-alpha-IL-10 ratio is controlled by the Nramp1 background of resistance/susceptibility and may account for the balance between apoptosis and macrophage survival.
 ...
PMID:TNF-alpha and IL-10 modulate the induction of apoptosis by virulent Mycobacterium tuberculosis in murine macrophages. 1022 55

The aly/aly (alymphoplasia) mice from a mutation of a colony of the C57BL/6J mouse strain, which has a systemic absence of lymph nodes and Peyer's patches, are deficient in both T- and B-cell-mediated immune functions. We have undertaken a comparison of susceptibility to Mycobacterium leprae of ALY (aly/aly, aly/+) mice with C57BL/6J mice. The aly/aly mouse was found to have an excellent high susceptibility to M. leprae with no distinction between female and male. The aly/+ mouse also was more susceptible to M. leprae at an earlier stage than the C57BL/6J mouse. Therefore, we examined and compared the cytokine gene expression and gamma interferon (IFN-gamma) induction in the splenocytes of ALY mice. The expression of interleukin 4 (IL-4), IL-10 and IL-12 mRNA was weakly stimulated with ML-lysate in inoculated aly/aly mice but IL-2, IL-6, IGIF/IL-18 and IFN-gamma mRNA were not observed. None of the cytokine genes used appeared, except the mRNA for IL-1-alpha, when uninfected cultured spleen cells were stimulated with ML-lysate. Also, IFN-gamma production was not induced. However, the appearance of these cytokine genes was observed when stimulated with concanavalin A (ConA), and IFN-gamma production was also induced in the culture supernatant by aly/+ and even aly/aly mice stimulated with ConA. To examine the reason why IFN-gamma cannot be produced by splenocytes of ALY mice inoculated with M. leprae, we detected cytokine gene expression and IFN-gamma induction in the presence of recombinant murine IL-12 or IGIF/IL-18. IL-2 mRNA expression was detected in all of the mice tested in the presence of IL-12 but not in aly/aly mice under IGIF/IL-18, and iNOS mRNA expression was not observed in aly/aly mice under IL-12 or IGIF/IL-18. IL-4 and IL-10 mRNA were detected by aly/aly mice only by exposure to IGIF/IL-18. In culture, the supernatant with ML antigens of the aly/aly mice did not produce IFN-gamma in spite of the presence of IL-12 and IGIF/IL-18, while IFN-gamma was weakly induced in aly/+ mice stimulated with ML-lysate and in the presence of IGIF/IL-18. Nevertheless, IFN-gamma production was observed in splenocytes of the aly/aly mice stimulated with ConA and also with IGIF/IL-18 plus anti-CD3 antibody. Our results suggest that ALY mice might be showing a high susceptibility to M. leprae because of deficient priming for activation of T cells with the leprosy bacilli infection. Moreover, it is possible that the phagocytic activities of the macrophages of ALY mice are also impaired.
 ...
PMID:Susceptibility to Mycobacterium leprae of ALY (alymphoplasia) mice and IFN-gamma induction in the culture supernatant of spleen cells. 1034 67

Mycobacterium tuberculosis CDC1551, a clinical isolate reported to be hypervirulent and to grow faster than other isolates, was compared with two other clinical isolates (HN60 and HN878) and two laboratory strains (H37Rv and Erdman). The initial (1-14 days) growth of CDC1551, HN60, HN878, and H37Rv was similar in the lungs of aerosol-infected mice, but growth of Erdman was slower. Thereafter, the growth rate of CDC1551 decreased relative to the other strains which continued to grow at comparable rates up to day 21. In the lungs of CDC1551-infected mice, small well-organized granulomas with high levels of TNF-alpha, IL-6, IL-10, IL-12, and IFN-gamma mRNA were apparent sooner than in lungs of mice infected with the other strains. CDC1551-infected mice survived significantly longer. These findings were confirmed in vitro. The growth rates of H37Rv and CDC1551 in human monocytes were the same, but higher levels of TNF-alpha, IL-10, IL-6, and IL-12 were induced in monocytes after infection with CDC1551 or by exposure of monocytes to lipid fractions from CDC1551. CD14 expression on the surface of the monocytes was up-regulated to a greater extent by exposure to the lipids of CDC1551. Thus, CDC1551 is not more virulent than other M. tuberculosis isolates in terms of growth in vivo and in vitro, but it induces a more rapid and robust host response.
 ...
PMID:Mycobacterium tuberculosis CDC1551 induces a more vigorous host response in vivo and in vitro, but is not more virulent than other clinical isolates. 1035 93

Mycobacterium tuberculosis bacilli readily activate CD4(+) and gammadelta T cells. CD4(+) and gammadelta T cells were compared for their ability to regulate IFN-gamma, TNF-alpha, and IL-10 production, cytokines with significant roles in the immune response to M. tuberculosis. PBMC from healthy tuberculin positive donors were stimulated with live M. tuberculosis-H37Ra. CD4(+) and gammadelta T cells were purified by negative selection and tested in response to autologous monocytes infected with M. tuberculosis. Both subsets produced equal amounts of secreted IFN-gamma. However, the precursor frequency of IFN-gamma secreting gammadelta T cells was half that of CD4(+) T cells, indicating that gammadelta T cells were more efficient producers of IFN-gamma than CD4(+) T cells. TNF-alpha production was markedly enhanced by addition of CD4(+) and gammadelta T cells to M. tuberculosis infected monocytes, and TNF-alpha was produced by both T cells and monocytes. No differences in TNF-alpha enhancement were noted between CD4(+) and gammadelta T cells. IL-10 production by M. tuberculosis infected monocytes was not modulated by CD4(+) or gammadelta T cells. Thus CD4(+) and gammadelta T cells had similar roles in differential regulation of IFN-gamma, TNF-alpha, and IL-10 secretion in response to M. tuberculosis infected monocytes. However, the interaction between T cells and infected monocytes differed for each cytokine. IFN-gamma production was dependent on antigen presentation and costimulators provided by monocytes. TNF-alpha levels were increased by addition of TNF-alpha produced by T cells and IL-10 production by monocytes was not modulated by CD4(+) or gammadelta T cells.
 ...
PMID:Differential regulation of IFN-gamma, TNF-alpha, and IL-10 production by CD4(+) alphabetaTCR+ T cells and vdelta2(+) gammadelta T cells in response to monocytes infected with Mycobacterium tuberculosis-H37Ra. 1035 76


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>