Henry W Boom

..These findings suggest that during BCG infection, the inflammation and sustained expression of CCL19 result in the recruitment, activation, and retention in the lung of DCs that can activate naïve CD4(+) T cells in situ...

..Thus, lung APC subsets differ in TLR expression, which may determine differences in responses to Mtb...

..We report detailed phylogenetic and genomic analyses devoted to prokaryotic rhomboids of an important genus, Mycobacterium...

..M. tuberculosis genetically modified to induce apoptosis is shown to be more effective in priming CD8(+) T cells in vivo and therefore may be a more effective vaccine against tuberculosis than the currently utilized M. bovis BCG vaccine...

..g., MTB, may immunologically silence macrophages and evade surveillance by both CD4(+) and CD8(+) T cells, promoting chronic infection...

..tuberculosis inhibits certain macrophage responses to IFN-gamma, particularly those related to MHC-II Ag presentation. This inhibition may promote M. tuberculosis evasion of T-cell responses and persistence of infection in tuberculosis...

..tuberculosis. However, downregulation of certain TLR responses may benefit the host by preventing detrimental excessive inflammation that may occur in the presence of persistent infection...

..Thus, infection with M. tuberculosis primes macrophages for the increased release of exosomes and microvesicles bearing M. tuberculosis peptide-MHC-II complexes that may generate antimicrobial T-cell responses...

..Immune activation in HIV is associated with progression to AIDS. Prior studies, focusing on persons with advanced HIV, have shown no decline in markers of cellular activation in response to TB therapy alone...

..Thus, lung APCs that harbor mycobacteria in vivo have decreased MHC-II expression relative to uninfected APCs from the same lung, possibly contributing to evasion of T cell responses...

..Chromatin remodeling at MHC2TA is a novel target of inhibition by Mtb. These mechanisms may diminish class II MHC expression by infected macrophages, contributing to immune evasion by Mtb...

..This study further illustrates the utility of such a model for disentangling complex traits...

..Prokaryotic HSPs are a potential source of microbial peptide Ags during phagocytic processing of bacteria during infection and could potentially be incorporated in vaccines to enhance presentation of peptides to CD8(+) T cells...

..Thus, Mtb LprA is a TLR2 agonist that induces cytokine responses and regulates APC function...

..We compared changes in T cell activation and function between patients receiving concurrent treatment for HIV-tuberculosis coinfection and those receiving treatment for tuberculosis alone...

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..Many of the genetic factors for each of these stages are part of the innate immune system...

..In conclusion, we demonstrate a glycolipid binding function of LprG that enhances recognition of triacylated MTB glycolipids by TLR2 and may affect glycolipid assembly or transport for bacterial cell wall biogenesis...

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..Thus, M. tuberculosis phagosomes with high levels of MHC-II and LAMP-1 and MIIC both have the potential to form peptide-MHC-II complexes from M. tuberculosis antigens in human macrophages...

..These findings provide a mechanism for M. tuberculosis persistence in macrophages...

..Using these techniques, we have demonstrated that phagosomes containing latex beads or Mycobacterium tuberculosis (MTB) contain components of the MHC II processing pathway and support the formation of peptide-MHC II complexes...

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..tuberculosis. These findings suggest that the mechanisms used by M. tuberculosis to inhibit phagosomal maturation differ from the mechanisms involved in modulating phagosome Ag processing...

..Our study provides evidence that Tregs suppress both anti-CD3 and antigen-driven Vdelta2+ T-cell activation. Antigen-specific Tregs may therefore contribute to the Vdelta2+ T-cell functional deficiencies observed in TB...

..ZAP-70 phosphorylation was decreased in the presence of M. tuberculosis glycolipids, indicating that M. tuberculosis glycolipids directly inhibited CD4(+) T-cell activation by interfering with proximal T-cell-receptor signaling...

..tuberculosis has subverted to create a niche for survival in infected macrophages and evasion of recognition by CD4(+) T cells...

..These findings suggest that IFN-alphabeta contributes to innate immunity to pulmonary mycobacterial infection by augmenting production of nitric oxide...

..T hybridomas restricted by human MHC represent convenient and powerful tools for the study of antigen processing by human APC...

..05). Haplotype analyses identified a significant risk haplotype in cathepsin X (CTSZ; p = 0.0281, odds ratio = 1.5493, 95% confidence interval [1.039, 2.320])...

..Cavitary disease and delayed culture conversion have been associated with relapse. Combining patient characteristics and measures of bacteriologic response might allow treatment shortening with current drugs in some patients...

..One patient in each arm relapsed. IL-2 did not enhance bacillary clearance or improvement in symptoms in human immunodeficiency virus-seronegative adults with drug-susceptible tuberculosis...

..Inhibition of IFN-gamma-induced CIITA by MTB 19-kDa lipoprotein may allow MTB to evade detection by CD4(+) T cells...

..Furthermore, these studies have not accounted for the influence of shared environment within households on TB risk, which may spuriously inflate estimates of heritability...

..CIITA types differ in regulation in various APCs under different stimuli, and the predominant type of CIITA varies at different stages of APC activation...

..Whether T cells can produce sufficient ATP is unknown. CD4(+) and CD8(+) T cells did not release sufficient ATP through either degranulation or lysis of bystander cells to restrict growth of Mycobacterium bovis BCG in monocytes...

..Chloroquine, by inhibiting membrane traffic, may increase association and retention of phosphoantigens with cell surface membrane molecules on macrophages...

..These data support the hypothesis that proteins encoded in the RD1 region are a major cause of necrosis and contribute significantly to the pathogenesis of the disease...

..Thus, susceptibility to tuberculosis may result from the ability of mycobacteria to interfere with MHC-II expression and antigen presentation by alveolar macrophages...

..Vdelta 2(+) T cells recognize phosphoantigens, such as bromohydrin pyrophosphate (BrHPP), and link innate and adaptive immunity...

..This is the first report of direct binding of a M. tuberculosis molecule to a receptor on human T cells resulting in a change in CD4+ T cell function...

..Inhibition of MHC-II Ag processing by mycobacterial lipoproteins may allow M. tuberculosis, within infected macrophages, to avoid recognition by CD4(+) T cells...

..Patients with cavitary disease had higher CFU levels than those without cavities and shorter DTPs. Within radiographic strata of moderately and far advanced tuberculosis, higher CFU counts were associated with cavitary disease...

..All three quinolones showed favorable pharmacokinetic and pharmacodynamic indices, with the most favorable results in this population being seen with levofloxacin at the comparative doses used...

..These data indicate that sputum cytokines correlate with disease activity during active TB of the lung and may serve as potential early markers for sputum conversion and response to anti-TB therapy...

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..Aim 3: To determine the ability of chemokines, CpG and cholera toxin to enhance innate and acquired immune defenses to M. bovis-BCG and M. Tuberculosis within lung. ..

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..These studies will provide insight into how MTB can regulate T cell responses to mycobacterial antigens. ..

..These studies will provide insight into how MTB can regulate T cell responses to mycobacterial antigens. ..

..These studies will provide insight into how MTB can regulate T cell responses to mycobacterial antigens. ..

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..These studies will provide insight into how MTB can regulate T cell responses to mycobacterial antigens. ..

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..These studies will provide insight into the regulation of human T cell subsets involved in protective immunity to M. tuberculosis, which is necessary for the design of improved vaccines, and immunotherapies for tuberculosis. ..

..Such information will not only increase our understanding of the host-pathogen relationship in tuberculosis but also is necessary for the design of vaccines and immunotherapeutic interventions for tuberculosis. ..

..tuberculosis. An understanding of the T cell response to this pathogen will contribute to the design of improved methods of prevention and diagnosis of tuberculosis. This is a health related project...

..tuberculosis, which is a major cause of morbidity and mortality worldwide. These studies are therefore, directly healthy-related...

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