• Disease
  • Mycobacterium
  • Mycobacterium Tuberculosis
  • Denise E Kirschner

    Prominent publications by Denise E Kirschner

    KOL Index score: 11612

    Macrophages in granulomas are both antimycobacterial effector and host cell for Mycobacterium tuberculosis, yet basic aspects of macrophage diversity and function within the complex structures of granulomas remain poorly understood. To address this, we examined myeloid cell phenotypes and expression of enzymes correlated with host defense in macaque and human granulomas. Macaque granulomas had upregulated inducible and endothelial NO synthase (iNOS and eNOS) and arginase (Arg1 and Arg2) ...

    Also Ranks for: Nitric Oxide |  tuberculous granulomas |  macrophage subsets |  host cell |  arg1 expression
    KOL Index score: 11570

    Lung granulomas are the pathologic hallmark of tuberculosis (TB). T cells are a major cellular component of TB lung granulomas and are known to play an important role in containment of Mycobacterium tuberculosis (Mtb) infection. We used cynomolgus macaques, a non-human primate model that recapitulates human TB with clinically active disease, latent infection or early infection, to understand functional characteristics and dynamics of T cells in individual granulomas. We sought to ...

    Also Ranks for: Tuberculosis Granuloma |  cell responses |  bacterial burden |  inflammatory cytokines |  cynomolgus macaques
    KOL Index score: 11218

    Multiple immune factors control host responses to Mycobacterium tuberculosis infection, including the formation of granulomas, which are aggregates of immune cells whose function may reflect success or failure of the host to contain infection. One such factor is TNF-α. TNF-α has been experimentally characterized to have the following activities in M. tuberculosis infection: macrophage activation, apoptosis, and chemokine and cytokine production. Availability of TNF-α within a granuloma ...

    Also Ranks for: Granuloma Formation |  computational model |  tuberculosis infection |  tnf α |  tumor necrosis factor
    KOL Index score: 11094

    We examine a model for the interaction of HIV with CD4+ T cells that considers four populations: uninfected T cells, latently infected T cells, actively infected T cells, and free virus. Using this model we show that many of the puzzling quantitative features of HIV infection can be explained simply. We also consider effects of AZT on viral growth and T-cell population dynamics. The model exhibits two steady states, an uninfected state in which no virus is present and an endemically ...

    Also Ranks for: Hiv Infection |  infected cells |  free virus |  viral growth |  steady state
    KOL Index score: 9497

    Mycobacterium tuberculosis is one of the world's most deadly human pathogens; an integrated understanding of how it successfully survives in its host is crucial to developing new treatment strategies. One notable characteristic of infection with M. tuberculosis is the formation of granulomas, aggregates of immune cells whose structure and function may reflect success or failure of the host to contain infection. One central regulator of host responses to infection, including granuloma ...

    Also Ranks for: Mycobacterium Tuberculosis |  host infection |  macrophage activation |  computational model |  granuloma formation
    KOL Index score: 9455

    Tuberculosis (TB), caused by Mycobacterium tuberculosis, continues to be a major global health problem. Lung granulomas are organized structures of host immune cells that function to contain the bacteria. Cytokine expression is a critical component of the protective immune response, but inappropriate cytokine expression can exacerbate TB. Although the importance of proinflammatory cytokines in controlling M. tuberculosis infection has been established, the effects of anti-inflammatory ...

    Also Ranks for: Lymph Nodes |  lung granulomas |  tuberculosis infection |  immune response |  bacterial control
    KOL Index score: 9140

    Previous experimental studies suggest that Mycobacterium tuberculosis inhibits a number of macrophage intracellular processes associated with antigen presentation, including antigen processing, MHC class II expression, trafficking of MHC class II molecules, and peptide-MHC class II binding. In this study, we investigate why multiple mechanisms have been observed. Specifically, we consider what purpose multiple mechanisms may serve, whether experimental protocols favor the detection of ...

    Also Ranks for: Antigen Presentation |  mycobacterium tuberculosis |  mhc class |  sensitivity analysis |  mathematical model
    KOL Index score: 9020

    Mathematical analysis is carried out that completely determines the global dynamics of a mathematical model for the transmission of human T-cell lymphotropic virus I (HTLV-I) infection and the development of adult T-cell leukemia (ATL). HTLV-I infection of healthy CD4(+) T cells takes place through cell-to-cell contact with infected T cells. The infected T cells can remain latent and harbor virus for several years before virus production occurs. Actively infected T cells can infect other ...

    Also Ranks for: Global Dynamics |  mathematical analysis |  infected cells |  atl progression |  htlvi infection
    KOL Index score: 8828

    Tuberculosis (TB) granulomas are organized collections of immune cells comprised of macrophages, lymphocytes and other cells that form in the lung as a result of immune response to Mycobacterium tuberculosis (Mtb) infection. Formation and maintenance of granulomas are essential for control of Mtb infection and are regulated in part by a pro-inflammatory cytokine, tumor necrosis factor-alpha (TNF). To characterize mechanisms that control TNF availability within a TB granuloma, we ...

    Also Ranks for: Tuberculosis Granuloma |  tumor necrosis |  immune cells |  mtb infection |  control tnf
    KOL Index score: 8745

    Interleukin-10 (IL-10) and tumor necrosis factor-α (TNF-α) are key anti- and pro-inflammatory mediators elicited during the host immune response to Mycobacterium tuberculosis (Mtb). Understanding the opposing effects of these mediators is difficult due to the complexity of processes acting across different spatial (molecular, cellular, and tissue) and temporal (seconds to years) scales. We take an in silico approach and use multi-scale agent based modeling of the immune response to Mtb, ...

    Also Ranks for: Tuberculosis Infection |  necrosis factor |  modeling predicts |  tnf α |  immune response
    KOL Index score: 8733

    Pulmonary infections and dysfunction are frequent outcomes during the development of immunodeficiency associated with human immunodeficiency virus type 1 (HIV-1) infection, and obtaining a better understanding of the immunologic changes that occur in lungs following HIV-1 infection will provide a foundation for the development of further intervention strategies. We sought here to identify changes in the pulmonary immune environment that arise during simian immunodeficiency virus (SIV) ...

    Also Ranks for: Lung Tissues |  simian immunodeficiency |  virus infection |  increased expression |  situ hybridization
    KOL Index score: 8697

    Infection with Mycobacterium tuberculosis is a major world health problem. An estimated 2 billion people are presently infected and the disease causes approximately 3 million deaths per year. After bacteria are inhaled into the lung, a complex immune response is triggered leading to the formation of multicellular structures termed granulomas. It is believed that the collection of host granulomas either contain bacteria resulting in a latent infection or are unable to do so, leading to ...

    Also Ranks for: Granuloma Formation |  immunological mycobacterium |  tuberculosis infection |  agentbased model |  active disease
    KOL Index score: 8432

    Tuberculosis is a worldwide health problem with 2 billion people infected with Mycobacterium tuberculosis (Mtb, the bacteria causing TB). The hallmark of infection is the emergence of organized structures of immune cells forming primarily in the lung in response to infection. Granulomas physically contain and immunologically restrain bacteria that cannot be cleared. We have developed several models that spatially characterize the dynamics of the host-mycobacterial interaction, and ...

    Also Ranks for: Granuloma Formation |  lung lymph node |  mycobacterium tuberculosis |  immune cells |  infection progression
    KOL Index score: 8404

    The human thymus exports newly generated T cells to the periphery. As no markers have been identified for these recent thymic emigrants (RTE), it is presently impossible to measure human thymic output. T cell receptor excision circles (TREC) have been recently used to assess thymic output during both health and disease. Using a mathematical model, we quantify age-dependent changes both in the number of RTE generated per day and in TREC concentration during an 80-year lifespan. Through ...

    Also Ranks for: Thymic Emigrants |  immunological receptors |  cell receptor |  excision circles |  gene rearrangement
    KOL Index score: 8352

    During most infections, the population of immune cells known as macrophages are key to taking up and killing bacteria as an integral part of the immune response. However, during infection with Mycobacterium tuberculosis (Mtb), host macrophages serve as the preferred environment for mycobacterial growth. Further, killing of Mtb by macrophages is impaired unless they become activated. Activation is induced by stimulation from bacterial antigens and inflammatory cytokines derived from ...

    Also Ranks for: Mycobacterium Tuberculosis |  mtb macrophages |  negative feedback |  immune cells |  mathematical model


    Denise E Kirschner: Influence Statistics

    Sample of concepts for which Denise E Kirschner is among the top experts in the world.
    Concept World rank
    nhp experimental data #1
    observed cases covid19 #1
    individual framework #1
    gastric disorders model #1
    biological node homing #1
    neutrophils granuloma dissemination #1
    thymus hiv1 #1
    granuloma formation tgfβ1 #1
    computational platform isoniazid #1
    workplace casual #1
    interactions mathematical #1
    tuberculosis fibrosis #1
    lesion sterilization #1
    poor patientadherence #1
    optimality immunological models #1
    host bacterial conditions #1
    peptidemhc levels #1
    current oral regimen #1
    multiple granulomas #1
    infection hostsim #1
    2d cellular movement #1
    macrophage activation levels #1
    gene perturbations granulomas #1
    validation biological datasets #1
    core population setting #1
    mechanisms granuloma #1
    immunological mycobacterium #1
    hypotheses primary host #1
    human rtes #1
    additional avenue #1
    endemic setting cambodia #1
    drug transcriptomics #1
    knowledge host #1
    immune response delays #1
    populations bacteriaproduced chemokine #1
    dynamics cholerae infection #1
    settings previous work #1
    drug dose strength #1
    granolomas lung #1
    granuloma macrophages mmt #1
    robustly efficacious vaccine #1
    multiscale modeling predicts #1
    hiv chemotherapy #1
    hostlevel outcomes #1
    cambodia endemic #1
    distinct heterogeneous #1
    challenging experimentally #1
    abm studies #1
    2d resolution gransim #1
    infection outcome factors #1

    Key People For Mycobacterium Tuberculosis

    Top KOLs in the world
    Clifton E Barry Barry
    mycobacterium tuberculosis mycolic acids cell wall
    William R Jacobs
    mycobacterium tuberculosis mycolic acids bacterial genes
    Stewart Thomas Cole
    mycobacterium tuberculosis escherichia coli clostridium perfringens
    Roland Brosch
    mycobacterium tuberculosis tubercle bacilli listeria monocytogenes
    Dick van Soolingen
    mycobacterium tuberculosis beijing genotype dna fingerprinting
    Brigitte Gicquel
    mycobacterium tuberculosis recombinant bcg human macrophages

    Denise E Kirschner:Expert Impact

    Concepts for whichDenise E Kirschnerhas direct influence:Mycobacterium tuberculosis,  Antigen presentation,  Granuloma formation,  Immune response,  Tuberculosis infection,  Lung granulomas,  Lymph node,  Washtenaw county.

    Denise E Kirschner:KOL impact

    Concepts related to the work of other authors for whichfor which Denise E Kirschner has influence:Mycobacterium tuberculosis,  Mathematical model,  Hiv infection,  Immune response,  Optimal control,  Helicobacter pylori,  Sensitivity analysis.



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    Department of Microbiology and Immunology, University of Michigan Medical School, 1150 W Medical Center Drive, 5641 Medical Science II, Ann Arbor, MI 48109-5620. Electronic address: kirschne@umich.edu. | University of Michigan Medical School - Depart