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Spontaneous phthiocerol dimycocerosate-deficient variants of Mycobacterium tuberculosis are susceptible to gamma interferon-mediated immunity

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Analysis of Stop-Gain and Frameshift Variants in Human Innate Immunity Genes

Jacques Fellay, Amalio Telenti, Istvan Bartha, Ioannis Xenarios

Loss-of-function variants in innate immunity genes are associated with Mendelian disorders in the form of primary immunodeficiencies. Recent resequencing projects report that stop-gains and frameshifts are collectively prevalent in humans and could be resp ...

Public Library Science2014

Specific fibroblastic niches in secondary lymphoid organs orchestrate distinct Notch-regulated immune responses

Freddy Radtke, Ute Koch, Nicolas Fasnacht, Floriane Auderset

Fibroblast-like cells of secondary lymphoid organs (SLO) are important for tissue architecture. In addition, they regulate lymphocyte compartmentalization through the secretion of chemokines, and participate in the orchestration of appropriate cell-cell in ...

Rockefeller University Press2014

Mycobacterium tuberculosis Requires Phosphate-Responsive Gene Regulation To Resist Host Immunity

John McKinney, Anna De Graff Tischler

Mycobacterium tuberculosis persists in the tissues of mammalian hosts despite inducing a robust immune response dominated by the macrophage-activating cytokine gamma interferon (IFN-gamma). We identified the M. tuberculosis phosphate-specific transport (Ps ...

American Society for Microbiology2013

Tuberculosis biomarkers discovery: developments, needs, and challenges

Stewart Cole

Biomarkers are indispensable to the development of new tuberculosis therapeutics and vaccines. The most robust biomarkers measure factors that are essential to the underlying pathological process of the disease being treated, and thus can capture the full ...

Elsevier Science Inc2013

Structural mechanism of cytosolic DNA sensing by cGAS

Andrea Ablasser

Cytosolic DNA arising from intracellular bacterial or viral infections is a powerful pathogen-associated molecular pattern (PAMP) that leads to innate immune host defence by the production of type I interferon and inflammatory cytokines. Recognition of cyt ...

2013

Induction of type I IFNs by intracellular DNA-sensing pathways

Andrea Ablasser

A successful antimicrobial immune response involves the coordinate action of cells and soluble factors, with the cytokine family of type I interferons (IFNs) having a central role. Type I IFNs are not only crucial in conferring immediate antimicrobial, mos ...

2012

Improving Immunogenicity of Subunit Vaccines Using Nanocarrier Systems

Armando Stano

New generation vaccines, which are subunit vaccines, have considerably improved safety profiles, but are often poorly immunogenic, especially when administered through mucosal routes. Also, the diversity of the mechanisms of action of infectious pathogens ...

EPFL2012

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In mycobacteria, CycA a D-serine, L-and D-alanine, and glycine transporter also functions in the uptake of D-cycloserine, an important second-line anti-tubercular drug. A single nucleotide polymorphism identified in the cycA gene of BCG was hypothesized to ...

Public Library of Science2012

Expression of the leptin receptor outside of bone marrow-derived cells regulates tuberculosis control and lung macrophage MHC expression

John McKinney

Leptin is a pleiotropic hormone proposed to link nutritional status to the development of strong Th1 immunity. Because Mycobacterium tuberculosis control is affected by starvation and diabetes, we studied the role of the leptin receptor in regulating disti ...

2011

L. monocytogenes is a Gram-positive intracellular pathogen that can cause serious disease, like septicemia and meningitis. It is detected in the cytosol by the innate immune system by sensing pathogen ligands. c-di-AMP has recently been shown to be one of ...

2011