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autophagy

  • Open Access
    Intracellular Density of <em>Wolbachia</em> Is Mediated by Host Autophagy and the Bacterial Cytoplasmic Incompatibility Gene <em>cifB</em> in a Cell Type-Dependent Manner in <span class="named-content genus-species" id="named-content-1">Drosophila melanogaster</span>
    Research Article | Host-Microbe Biology
    Intracellular Density of Wolbachia Is Mediated by Host Autophagy and the Bacterial Cytoplasmic Incompatibility Gene cifB in a Cell Type-Dependent Manner in Drosophila melanogaster

    Autophagy is a eukaryotic intracellular degradation pathway which can act as an innate immune response to eliminate pathogens. Conversely, pathogens can evolve proteins which modulate the autophagy pathway to subvert degradation and establish an infection. Wolbachia, a vertically transmitted obligate endosymbiont which infects up to 40% of insect species, is negatively regulated by autophagy in whole animals, but the specific...

    Mark Deehan, Weiwei Lin, Benjamin Blum, Andrew Emili, Horacio Frydman
  • Open Access
    ISG15 Connects Autophagy and IFN-γ-Dependent Control of <span class="named-content genus-species" id="named-content-1">Toxoplasma gondii</span> Infection in Human Cells
    Research Article | Host-Microbe Biology
    ISG15 Connects Autophagy and IFN-γ-Dependent Control of Toxoplasma gondii Infection in Human Cells

    Interferon(s) provide the primary defense against intracellular pathogens, a property ascribed to their ability to upregulate interferon-stimulated genes. Due to the sequestered niche occupied by Toxoplasma gondii, the host has elaborated intricate ways to target the parasite within its vacuole. One such mechanism is the recognition by a noncanonical autophagy pathway...

    Jaya Bhushan, Joshua B. Radke, Yi-Chieh Perng, Michael Mcallaster, Deborah J. Lenschow, Herbert W. Virgin, L. David Sibley
  • Open Access
    CD4<sup>+</sup> T Cell-Mimicking Nanoparticles Broadly Neutralize HIV-1 and Suppress Viral Replication through Autophagy
    Research Article | Therapeutics and Prevention
    CD4+ T Cell-Mimicking Nanoparticles Broadly Neutralize HIV-1 and Suppress Viral Replication through Autophagy

    HIV-1 is a major global health challenge. The development of an effective vaccine and/or a therapeutic cure is a top priority. The creation of vaccines that focus an antibody response toward a particular epitope of a protein has shown promise, but the genetic diversity of HIV-1 hinders this progress. Here we developed an approach using nanoengineered CD4+ T cell membrane-coated nanoparticles (TNP). Not only do TNP effectively...

    Gang Zhang, Grant R. Campbell, Qiangzhe Zhang, Erin Maule, Jonathan Hanna, Weiwei Gao, Liangfang Zhang, Stephen A. Spector
  • Open Access
    Guanylate Binding Proteins Restrict <span class="named-content genus-species" id="named-content-1">Leishmania donovani</span> Growth in Nonphagocytic Cells Independent of Parasitophorous Vacuolar Targeting
    Research Article | Host-Microbe Biology
    Guanylate Binding Proteins Restrict Leishmania donovani Growth in Nonphagocytic Cells Independent of Parasitophorous Vacuolar Targeting

    The obligate intracellular parasite Leishmania causes the disease leishmaniasis, which is transmitted to mammalian hosts, including humans, via the sandfly vector. Following the bite-induced breach of the skin barrier, Leishmania is known to live and replicate predominantly inside professional phagocytes. Although Leishmania is also able to infect nonphagocytic cells, nonphagocytic cells support limited...

    Arun Kumar Haldar, Utsav Nigam, Masahiro Yamamoto, Jörn Coers, Neena Goyal
  • Open Access
    Integrin α5β1, as a Receptor of Fibronectin, Binds the FbaA Protein of Group A <em>Streptococcus</em> To Initiate Autophagy during Infection
    Research Article | Host-Microbe Biology
    Integrin α5β1, as a Receptor of Fibronectin, Binds the FbaA Protein of Group A Streptococcus To Initiate Autophagy during Infection

    Autophagy is generally considered a strategy used by the innate immune system to eliminate invasive pathogens through capturing and transferring them to lysosomes. Currently, researchers pay more attention to how virulence factors secreted by GAS regulate the autophagic process. Here, we provide the first evidence that the structural protein FbaA of M1 GAS strain SF370 is a potent inducer of autophagy in epithelial cells. Furthermore,...

    Jiachao Wang, Meiqi Meng, Miao Li, Xiaofei Guan, Jianguo Liu, Xue Gao, Qingqing Sun, Jinquan Li, Cuiqing Ma, Lin Wei
  • Open Access
    Translation Inhibition by Rocaglates Activates a Species-Specific Cell Death Program in the Emerging Fungal Pathogen <span class="named-content genus-species" id="named-content-1">Candida auris</span>
    Research Article | Therapeutics and Prevention
    Translation Inhibition by Rocaglates Activates a Species-Specific Cell Death Program in the Emerging Fungal Pathogen Candida auris

    Emergence of the fungal pathogen Candida auris has ignited intrigue and alarm within the medical community and the public at large. This pathogen is unusually resistant to antifungals, threatening to overwhelm current management options. By screening a library of structurally diverse molecules, we found that...

    Kali R. Iyer, Luke Whitesell, John A. Porco, Thomas Henkel, Lauren E. Brown, Nicole Robbins, Leah E. Cowen
  • Open Access
    Autoantibody-Mediated Erythrophagocytosis Increases Tuberculosis Susceptibility in HIV Patients
    Research Article | Host-Microbe Biology
    Autoantibody-Mediated Erythrophagocytosis Increases Tuberculosis Susceptibility in HIV Patients

    HIV infection significantly increases TB susceptibility due to CD4 T-cell loss and macrophage dysfunction. Although it is relatively clear that CD4 T-cell loss represents a direct effect of HIV infection, the mechanism underlying how HIV infection dampens macrophage function is unknown. Here, we show that HIV infection enhances autoantibody-mediated erythrophagocytosis, which dampens macrophage bactericidal activity against TB by...

    Youchao Dai, Yi Cai, Xin Wang, Jialou Zhu, Xiaoqian Liu, Houming Liu, Linghua Li, Yinze Zhang, Shengze Liu, Zhihua Wen, Carl G. Feng, Xinchun Chen, Xiaoping Tang
  • Open Access
    MicroRNA-889 Inhibits Autophagy To Maintain Mycobacterial Survival in Patients with Latent Tuberculosis Infection by Targeting TWEAK
    Research Article | Host-Microbe Biology
    MicroRNA-889 Inhibits Autophagy To Maintain Mycobacterial Survival in Patients with Latent Tuberculosis Infection by Targeting TWEAK

    TB remains a leading cause of morbidity and mortality worldwide. Approximately one-quarter of the world’s population has latent TB infection. TWEAK is a multiple-function cytokine and may be used as a target for the treatment of rheumatic diseases, cardiovascular diseases, and renal diseases. Here, we demonstrated a novel relationship between TWEAK and activation of the autophagic machinery which promotes antimycobacterial immunity....

    Der-Yuan Chen, Yi-Ming Chen, Chin-Fu Lin, Che-Min Lo, Hung-Jen Liu, Tsai-Ling Liao
  • Open Access
    Role of <em>Toxoplasma gondii</em> Chloroquine Resistance Transporter in Bradyzoite Viability and Digestive Vacuole Maintenance
    Research Article | Host-Microbe Biology
    Role of Toxoplasma gondii Chloroquine Resistance Transporter in Bradyzoite Viability and Digestive Vacuole Maintenance

    Individuals chronically infected with the intracellular parasite Toxoplasma gondii are at risk of experiencing reactivated disease that can result in progressive loss of vision. No effective treatments exist for chronic toxoplasmosis due in part to a poor understanding of the biology underlying chronic infection and a lack of well-validated potential targets. We show...

    Geetha Kannan, Manlio Di Cristina, Aric J. Schultz, My-Hang Huynh, Fengrong Wang, Tracey L. Schultz, Matteo Lunghi, Isabelle Coppens, Vern B. Carruthers
  • Open Access
    The ESCRT-Related ATPase Vps4 Is Modulated by Interferon during Herpes Simplex Virus 1 Infection
    Research Article | Host-Microbe Biology
    The ESCRT-Related ATPase Vps4 Is Modulated by Interferon during Herpes Simplex Virus 1 Infection

    Neurons rely on IFNs and autophagy as major defenses against viral infections, and HSV must overcome such defenses in order to replicate. In addition to controlling host immunity, HSV must also control host membranes in order to complete its life cycle. HSV uses the host ESCRT membrane scission machinery for viral production and transport. Here we present evidence of a new IFN-dependent mechanism used by the host to prevent ESCRT...

    Jorge Ruben Cabrera, Richard Manivanh, Brian J. North, David A. Leib

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