Igor Kramnik
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View article: Save the mouse! Non-lethal, repeated blood transcriptome profiling in murine disease models 3386
Save the mouse! Non-lethal, repeated blood transcriptome profiling in murine disease models 3386 Open
Description Murine disease models can reveal mechanisms and allow testing of drug/vaccine interventions. Current approaches often rely on evaluation after euthanasia, with large numbers of animals needed for time course and dose-response s…
View article: Dysplastic lung repair fosters a tuberculosis-promoting microenvironment through maladaptive macrophage polarization
Dysplastic lung repair fosters a tuberculosis-promoting microenvironment through maladaptive macrophage polarization Open
Pulmonary TB that develops in immunocompetent adult humans is responsible for approximately 85% of the disease burden and is central for Mtb transmission. Most humans contain Mtb infection within primary granulomatous lesions, but in certa…
View article: Lipid peroxidation and type I interferon coupling fuels pathogenic macrophage activation causing tuberculosis susceptibility
Lipid peroxidation and type I interferon coupling fuels pathogenic macrophage activation causing tuberculosis susceptibility Open
A quarter of the human population is infected with Mycobacterium tuberculosis , but less than 10% of those infected develop pulmonary TB. We developed a genetically defined sst1-susceptible mouse model that uniquely reproduces a defining f…
View article: Lipid Peroxidation and Type I Interferon Coupling Fuels Pathogenic Macrophage Activation Causing Tuberculosis Susceptibility
Lipid Peroxidation and Type I Interferon Coupling Fuels Pathogenic Macrophage Activation Causing Tuberculosis Susceptibility Open
A quarter of human population is infected with Mycobacterium tuberculosis, but less than 10% of those infected develop pulmonary TB. We developed a genetically defined sst1-susceptible mouse model that uniquely reproduces a defining featur…
View article: Lipid Peroxidation and Type I Interferon Coupling Fuels Pathogenic Macrophage Activation Causing Tuberculosis Susceptibility
Lipid Peroxidation and Type I Interferon Coupling Fuels Pathogenic Macrophage Activation Causing Tuberculosis Susceptibility Open
A quarter of human population is infected with Mycobacterium tuberculosis, but less than 10% of those infected develop pulmonary TB. We developed a genetically defined sst1-susceptible mouse model that uniquely reproduces a defining featur…
View article: Elimination of senescent cells with senolytic host-directed therapy reduces tuberculosis progression in mice
Elimination of senescent cells with senolytic host-directed therapy reduces tuberculosis progression in mice Open
By eliciting lung necrosis, which enhances aerosol transmission, Mycobacterium tuberculosis ( Mtb ) sustains its long-term survival as a human pathogen. In studying the human-like necrotic granuloma lesions characteristic of Mtb -infected …
View article: Protocol for Developing a Mouse Model of Post Primary Pulmonary Tuberculosis after Hematogenous Spread in Native Lungs and Lung Implants
Protocol for Developing a Mouse Model of Post Primary Pulmonary Tuberculosis after Hematogenous Spread in Native Lungs and Lung Implants Open
Summary This protocol describes a mouse model of post-primary pulmonary tuberculosis (PTB) that develops after hematogenous spread from the primary lesion in native lungs and subcutaneous lung implants. It demonstrates that virulent Mycoba…
View article: Protocol for 3D multiplexed fluorescent imaging of pulmonary TB lesions using Opal-TSA dyes for signal amplification
Protocol for 3D multiplexed fluorescent imaging of pulmonary TB lesions using Opal-TSA dyes for signal amplification Open
To detect multiple protein markers, here we present a protocol for imaging pulmonary tuberculosis (PTB) lesions from murine lungs using Opal-tyramide signal amplification (TSA) conjugated fluorescent dyes in free-floating formalin-fixed th…
View article: 3D Multiplexed Immunohistochemistry Using Opal-TSA Amplification for Enhanced Imaging of Pulmonary TB Lesions
3D Multiplexed Immunohistochemistry Using Opal-TSA Amplification for Enhanced Imaging of Pulmonary TB Lesions Open
Summary Mycobacterium tuberculosis hijacks the host immune system and persists for several years before the onset of active disease. Spatial characterization of epithelial compartments, immune cell populations and bacteria simultaneously w…
View article: B cells in perivascular and peribronchiolar granuloma-associated lymphoid tissue and B-cell signatures identify asymptomatic <i>Mycobacterium tuberculosis</i> lung infection in Diversity Outbred mice
B cells in perivascular and peribronchiolar granuloma-associated lymphoid tissue and B-cell signatures identify asymptomatic <i>Mycobacterium tuberculosis</i> lung infection in Diversity Outbred mice Open
Because most humans resist Mycobacterium tuberculosis infection, there is a paucity of lung samples to study. To address this gap, we infected Diversity Outbred mice with M. tuberculosis and studied the lungs of mice in different disease s…
View article: Systems genetics uncover new loci containing functional gene candidates in Mycobacterium tuberculosis-infected Diversity Outbred mice
Systems genetics uncover new loci containing functional gene candidates in Mycobacterium tuberculosis-infected Diversity Outbred mice Open
Mycobacterium tuberculosis infects two billion people across the globe, and results in 8–9 million new tuberculosis (TB) cases and 1–1.5 million deaths each year. Most patients have no known genetic basis that predisposes them to disease. …
View article: Lipid Peroxidation and Type I Interferon Coupling Fuels Pathogenic Macrophage Activation Causing Tuberculosis Susceptibility
Lipid Peroxidation and Type I Interferon Coupling Fuels Pathogenic Macrophage Activation Causing Tuberculosis Susceptibility Open
A quarter of human population is infected with Mycobacterium tuberculosis, but less than 10% of those infected develop pulmonary TB. We developed a genetically defined sst1-susceptible mouse model that uniquely reproduces a defining featur…
View article: Systems genetics uncover new loci containing functional gene candidates in<i>Mycobacterium tuberculosis</i>-infected Diversity Outbred mice
Systems genetics uncover new loci containing functional gene candidates in<i>Mycobacterium tuberculosis</i>-infected Diversity Outbred mice Open
Mycobacterium tuberculosis, the bacillus that causes tuberculosis (TB), infects 2 billion people across the globe, and results in 8-9 million new TB cases and 1-1.5 million deaths each year. Most patients have no known genetic basis that p…
View article: Aberrant macrophage activation and maladaptive lung repair promote tuberculosis progression uniquely in the lung
Aberrant macrophage activation and maladaptive lung repair promote tuberculosis progression uniquely in the lung Open
Pulmonary tuberculosis (PTB) represents 85% of the disease burden caused by Mycobacterium tuberculosis (Mtb) and promotes aerosol transmission infecting about a quarter of people globally. Most Mtb infections are effectively limited within…
View article: Cell state transition analysis identifies interventions that improve control of <i>Mycobacterium tuberculosis</i> infection by susceptible macrophages
Cell state transition analysis identifies interventions that improve control of <i>Mycobacterium tuberculosis</i> infection by susceptible macrophages Open
Understanding cell state transitions and purposefully controlling them to improve therapies is a longstanding challenge in biological research and medicine. Here, we identify a transcriptional signature that distinguishes activated macroph…
View article: Perivascular and peribronchiolar granuloma-associated lymphoid tissue and B-cell gene expression pathways identify asymptomatic<i>Mycobacterium tuberculosis</i>lung infection in Diversity Outbred mice
Perivascular and peribronchiolar granuloma-associated lymphoid tissue and B-cell gene expression pathways identify asymptomatic<i>Mycobacterium tuberculosis</i>lung infection in Diversity Outbred mice Open
Humans are highly genetically diverse, and most are resistant to Mycobacterium tuberculosis. However, lung tissue from genetically resistant humans is not readily available to identify potential mechanisms of resistance. To address this, w…
View article: Adjunctive Integrated Stress Response Inhibition Accelerates Tuberculosis Clearance in Mice
Adjunctive Integrated Stress Response Inhibition Accelerates Tuberculosis Clearance in Mice Open
Necrosis of lung lesions is a hallmark of tuberculosis (TB) that promotes bacterial growth, dissemination, and transmission. This process is driven by the persistent hyperactivation of the integrated stress response (ISR) pathway.
View article: Cell state transition analysis identifies interventions that improve control of<i>M. tuberculosis</i>infection by susceptible macrophages
Cell state transition analysis identifies interventions that improve control of<i>M. tuberculosis</i>infection by susceptible macrophages Open
Understanding cell state transitions and purposefully controlling them to improve therapies is a longstanding challenge in biological research and medicine. Here, we identify a transcriptional signature that distinguishes activated macroph…
View article: Progression and Dissemination of Pulmonary Mycobacterium Avium Infection in a Susceptible Immunocompetent Mouse Model
Progression and Dissemination of Pulmonary Mycobacterium Avium Infection in a Susceptible Immunocompetent Mouse Model Open
Pulmonary infections caused by the group of nontuberculosis mycobacteria (NTM), Mycobacterium avium complex (MAC), are a growing public health concern with incidence and mortality steadily increasing globally. Granulomatous inflammation is…
View article: Adjunctive inhibition of the integrated stress response pathway accelerates bacterial clearance in a mouse model of tuberculosis
Adjunctive inhibition of the integrated stress response pathway accelerates bacterial clearance in a mouse model of tuberculosis Open
Tuberculosis (TB) is a devastating infectious disease that continues to cause millions of human deaths every year. Even though most cases of TB can be cured with a 6-month antibiotic combination therapy, these long treatment durations have…
View article: CXCL1: A new diagnostic biomarker for human tuberculosis discovered using Diversity Outbred mice
CXCL1: A new diagnostic biomarker for human tuberculosis discovered using Diversity Outbred mice Open
More humans have died of tuberculosis (TB) than any other infectious disease and millions still die each year. Experts advocate for blood-based, serum protein biomarkers to help diagnose TB, which afflicts millions of people in high-burden…
View article: Channeling macrophage polarization by rocaglates increases macrophage resistance to Mycobacterium tuberculosis
Channeling macrophage polarization by rocaglates increases macrophage resistance to Mycobacterium tuberculosis Open
Macrophages contribute to host immunity and tissue homeostasis via alternative activation programs. M1-like macrophages control intracellular bacterial pathogens and tumor progression. In contrast, M2-like macrophages shape reparative micr…