• Disease
  • Mycobacterium
  • Mycobacterium Tuberculosis
  • Joanne L Flynn

    Prominent publications by JoAnne L Flynn

    KOL Index score: 16653

    It is estimated that one-third of the world's population is infected with Mycobacterium tuberculosis. Infection typically remains latent, but it can reactivate to cause clinical disease. The only vaccine, Mycobacterium bovis bacillus Calmette-Guérin (BCG), is largely ineffective, and ways to enhance its efficacy are being developed. Of note, the candidate booster vaccines currently under clinical development have been designed to improve BCG efficacy but not prevent reactivation of ...

    Also Ranks for: Tuberculosis Infection |  multistage vaccine |  bcg h56 |  cynomolgus macaques |  clinical disease
    KOL Index score: 15204

    IFN-γ is necessary in both humans and mice for control of Mycobacterium tuberculosis. CD4 T cells are a significant source of IFN-γ during acute infection in mice and are required for control of bacterial growth and host survival. However, several other types of cells can and do produce IFN-γ during the course of the infection. We sought to determine whether IFN-γ from sources other than CD4 T cells was sufficient to control M. tuberculosis infection and whether CD4 T cells had a role in ...

    Also Ranks for: Tuberculosis Infection |  cd4 cells |  ifn γ |  knockout mice |  transgenic mycobacterium
    KOL Index score: 14616

    Several lines of evidence suggest that CD8 T cells are important in protection against tuberculosis. To understand the function of this cell population in the immune response against Mycobacterium tuberculosis, T cells from lungs of M. tuberculosis-infected mice were examined by flow cytometry. The kinetics of the appearance of CD8 T cells in lungs of infected mice closely paralleled that of CD4 T cells. Both CD4(+) and CD8(+) T cells displaying an activated phenotype were found in the ...

    Also Ranks for: Cd8 Cells |  infected mice |  mycobacterium tuberculosis |  gamma interferon ifngamma |  immune response
    KOL Index score: 13042

    The control of acute and chronic Mycobacterium tuberculosis infection is dependent on CD4(+) T cells. In a variety of systems CD8(+) T cell effector responses are dependent on CD4(+) T cell help. The development of CD8(+) T cell-mediated immune responses in the absence of CD4(+) T cells was investigated in a murine model of acute tuberculosis. In vitro and in vivo, priming of mycobacteria-specific CD8(+) T cells was unaffected by the absence of CD4(+) T cells. Infiltration of CD8(+) T ...

    Also Ranks for: Cd4 Cells |  mycobacterium tuberculosis |  wildtype mice |  lymphocytes cytotoxic |  hiv infection
    KOL Index score: 12913

    The contribution of CD8(+) T cells to the control of tuberculosis has been studied primarily during acute infection in mouse models. Memory or recall responses in tuberculosis are less well characterized, particularly with respect to the CD8 T-cell subset. In fact, there are published reports that CD8(+) T cells do not participate in the memory immune response to Mycobacterium tuberculosis. We examined the CD8(+) T-cell memory and local recall response to M. tuberculosis. To establish a ...

    Also Ranks for: Cd8 Cells |  memory immune response |  mycobacterium tuberculosis tuberculosis |  immune mice |  gamma interferon
    KOL Index score: 12690

    OBJECTIVE: An increased risk of tuberculosis has been documented in humans treated with tumor necrosis factor alpha (TNFalpha)-neutralizing agents. In murine models, impaired signaling by TNF causes exacerbation of both acute and chronic infection associated with aberrant granuloma formation and maintenance. This study was undertaken to investigate immune modulation in the setting of TNF neutralization in primary and latent tuberculosis in a non-human primate model.

    METHODS: Cynomolgus ...

    Also Ranks for: Tuberculosis Infection |  necrosis factor |  monoclonal antibodies |  latent mycobacterium |  tnf neutralization
    KOL Index score: 12422

    Granulomas, focal accumulations of immune cells, form in the lung during Mycobacterium tuberculosis infection. Chemokines, chemotactic cytokines, are logical candidates for inducing migration of T lymphocytes and monocytes to and within the lung. TNF influences chemokine expression in some models. TNF-deficient mice infected with M. tuberculosis are highly susceptible to disease, and granuloma formation is inhibited. Through in vitro assays, we demonstrate that neutralization of TNF in ...

    Also Ranks for: Mycobacterium Tuberculosis Infection |  chemokine expression |  granuloma formation |  immune cells |  tnfdeficient mice
    KOL Index score: 12375

    The development of a portfolio of COVID-19 vaccines to vaccinate the global population remains an urgent public health imperative1. Here we demonstrate the capacity of a subunit vaccine, comprising the SARS-CoV-2 spike protein receptor-binding domain displayed on an I53-50 protein nanoparticle scaffold (hereafter designated RBD–NP), to stimulate robust and durable neutralizing-antibody responses and protection against SARS-CoV-2 in rhesus macaques. We evaluated five adjuvants including ...

    Also Ranks for: Protective Immunity |  neutralizing antibodies |  spike glycoprotein |  protection sarscov2 |  covid19 vaccines
    KOL Index score: 12359

    Tuberculosis is a major cause of death in much of the world. Current estimates are that one-third of the world's population is infected with Mycobacterium tuberculosis. Most infected persons control the infection but in many cases may not eliminate the organism. Reactivation of this clinically latent infection is responsible for a large proportion of active tuberculosis cases. A major risk factor for reactivation of latent tuberculosis is HIV infection, suggesting a role for the CD4(+) T ...

    Also Ranks for: Nitric Oxide |  interferon γ |  cd4 cells |  latent tuberculosis |  macrophage activation
    KOL Index score: 12321

    CD8+ T lymphocytes have been implicated in the protective immune response against human and murine tuberculosis. However, the functional role that this cell subset plays during the resolution of infection remains controversial. In this study, we demonstrate the presence of Mycobacterium tuberculosis-specific CD8+ CTL in the lungs and lung-draining lymph nodes of mice infected with M. tuberculosis via the aerosol or i.v. route. These cells expressed perforin in vivo and specifically ...

    Also Ranks for: Infected Macrophages |  cytotoxic tuberculosis |  cd8 ctl |  inbred c57bl mice |  protective immune response
    KOL Index score: 11933

    The chemokine receptor CXCR3 plays a significant role in regulating the migration of Th1 cells. Given the importance of Th1 immunity in the control of tuberculous infection, the results of the present study demonstrating that CXCR3-deficient BALB/c mice are more resistant to Mycobacterium tuberculosis, compared with wild-type mice, is surprising. This enhanced resistance manifests in the chronic but not the acute phase of infection. Remarkable differences in the cellular composition of ...

    Also Ranks for: Tuberculosis Infection |  chemokine receptor |  cxcr3 mice |  chronic phase |  th1 cells
    KOL Index score: 11903

    In 2017 over 550,000 estimated new cases of multi-drug/rifampicin resistant tuberculosis (MDR/RR-TB) occurred, emphasizing a need for new treatment strategies. Linezolid (LZD) is a potent antibiotic for drug-resistant Gram-positive infections and is an effective treatment for TB. However, extended LZD use can lead to LZD-associated host toxicities, most commonly bone marrow suppression. LZD toxicities may be mediated by IL-1, an inflammatory pathway important for early immunity during M. ...

    Also Ranks for: Linezolid Therapy |  lzd macaques |  tuberculosis infection il1 |  early immunity |  inflammatory pathway
    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


    JoAnne L Flynn: Influence Statistics

    Sample of concepts for which JoAnne L Flynn is among the top experts in the world.
    Concept World rank
    control mycobacterium tuberculosis #1
    infected animals tuberculosis #1
    increases cd4tbet cells #1
    ribosomal granuloma #1
    spectrum granuloma level #1
    monkeys bcg #1
    fibrotic granulomas fibrosis #1
    tuberculosis discussed #1
    tuberculosis elispot #1
    macaque models tuberculosis #1
    purified grzb #1
    cynomolgus macaques effects #1
    insights host #1
    enzymelinked immunospot elispot #1
    computational models antibiotics #1
    eicosanoids proinflammatory effects #1
    granuloma behaviors #1
    miru cnv mtb #1
    immunomodulatory therapy challenges #1
    tissuebased experiments #1
    28 nonhuman primates #1
    fascicularis mycobacterium #1
    tuberculosisinfected cd4 #1
    sarscov2exposed nhps #1
    adalimumab infection #1
    antitb drug treatments #1
    sivm tuberculosis #1
    coinfection hivinfected individuals #1
    responses sterile granulomas #1
    bacterial state outcome #1
    latent infection severity #1
    greater interferon #1
    breath nonhuman primates #1
    lzd host toxicities #1
    influences chemokine #1
    ccr5transgenic knockout mice #1
    tnf chemokine expression #1
    failure granulomas #1
    infection ccr2 mice #1
    disease discernible #1
    siv infection siv #1
    m3restricted manner #1
    hallmark mtb infection #1
    formation granulomas #1
    monkeys tnf #1
    pittsburgh digital radiography #1
    factors latent animals #1
    critical bactericidal cells #1
    mmia serodetection #1
    mycobacterium tuberculosis active #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

    JoAnne L Flynn:Expert Impact

    Concepts for whichJoAnne L Flynnhas direct influence:Mycobacterium tuberculosis,  Tuberculosis infection,  Cynomolgus macaques,  Latent tuberculosis,  Lymph nodes,  Lung granulomas,  Mycobacterium tuberculosis infection,  Nonhuman primates.

    JoAnne L Flynn:KOL impact

    Concepts related to the work of other authors for whichfor which JoAnne L Flynn has influence:Mycobacterium tuberculosis,  Immune response,  Dendritic cells,  Nitric oxide,  Mycobacterial infection,  Necrosis factor,  Animal models.



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    Department of Microbiology and Molecular Genetics and the Center for Vaccine Research, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA | Center for Vaccine Research, University of Pittsburgh, Pittsburgh, Pennsylvania, United States o