Immune Regulation News Volume 4.28 | Jul 27 2012

Bacterial Virulence Proteins as Tools to Rewire Kinase Pathways in Yeast and Immune Cells
Researchers exploited two effector proteins, the Shigella flexneri OspF protein3 and Yersinia pestis YopH protein4, to rewire kinase-mediated responses systematically both in yeast and mammalian immune cells. [Nature] Abstract | Press Release

TRIF Licenses Caspase-11-Dependent NLRP3 Inflammasome Activation by Gram-Negative Bacteria
Though it is well recognized that the immune response during Gram-negative bacterial infection is initiated after the recognition of endotoxin by Toll-like receptor 4, the molecular mechanisms underlying the detrimental inflammatory response during Gram-negative bacteremia remain poorly defined. The authors identified a TRIF pathway that licenses NLRP3 inflammasome activation by all Gram-negative bacteria. [Cell] Abstract

Compartmentalized Control of Skin Immunity by Resident Commensals
Researchers report an autonomous role for the skin microbiota in controlling the local inflammatory milieu and tuning resident T lymphocyte function. They found that protective immunity to a cutaneous pathogen was critically dependent on the skin but not gut microbiota. [Science] Abstract | Press Release

Adenylate Cyclases of Trypanosoma brucei Inhibit the Innate Immune Response of the Host
Researchers found that activation of trypanosome adenylate cyclase resulting from parasite phagocytosis by liver myeloid cells inhibited the synthesis of the trypanosome-controlling cytokine tumor necrosis factor-α through activation of protein kinase A in these cells. [Science] Abstract

Recognition of CD1d-Sulfatide Mediated by a Type II Natural Killer T Cell Antigen Receptor
Scientists report a basis for how a type II natural killer T cell (NKT cell) T cell antigen receptor (TCR), XV19, recognized CD1d-sulfatide. The XV19 TCR bound orthogonally above the A′ pocket of CD1d, in contrast to the parallel docking of type I NKT cell TCRs over the F′ pocket of CD1d. [Nat Immunol] Abstract

Type II Natural Killer T Cells Use Features of Both Innate-Like and Conventional T Cells to Recognize Sulfatide Self Antigens
Researchers describe the structure of a type II natural killer T cell T cell antigen receptor in complex with CD1d-lysosulfatide. [Nat Immunol] Abstract

Silencing of Irf7 Pathways in Breast Cancer Cells Promotes Bone Metastasis through Immune Escape
Researchers found that, in mice deficient in the interferon (IFN) receptor or in natural killer and CD8⁺ T cell responses, metastasis was accelerated, indicating that Irf7-driven suppression of metastasis was reliant on IFN signaling to host immune cells. [Nat Med] Abstract | Press Release

Cytomegalovirus Impairs Antiviral CD8⁺ T Cell Immunity by Recruiting Inflammatory Monocytes
The authors report that the murine cytomegalovirus-encoded CC chemokine, MCK2, enhanced CCR2-dependent recruitment of these cells to modulate antiviral immunity, impairing virus-specific CD8⁺ T cell expansion and differentiation into effector cytotoxic T lymphocytes, thus reducing the capacity to eliminate viral antigen-bearing cells and slowing viral clearance. [Immunity] Abstract

The RIG-I-Like Receptor LGP2 Controls CD8⁺ T Cell Survival and Fitness
Researchers showed that the RIG-I-like receptor LGP2 was not essential for induction of innate immune defenses, but rather was required for controlling antigen-specific CD8⁺ T cell survival and fitness during peripheral T cell-number expansion in response to virus infection. [Immunity] Abstract

Airway CD8⁺ T Cells Induced by Pulmonary DNA Immunization Mediate Protective Anti-Viral Immunity
The authors showed that pulmonary immunization using plasmid DNA formulated with the polymer polyethyleneimine induced antigen-specific CD8⁺ T cells in the airways that persisted long after antigen local clearance. [Mucosal Immunol] Abstract

Rheumatoid Arthritis New Major Clinical Target after Mesoblast Obtains Positive Results in Inflammatory Arthritis
Regenerative medicine company Mesoblast Limited announced positive results in a large animal model of rheumatoid arthritis following a single intravenous injection of its proprietary allogeneic, or “off-the-shelf”, immunomodulatory adult Mesenchymal Precursor Cells. [Mesoblast, Ltd.] Press Release

Fraundhofer IZI Receives Official Certification for Manufacturing of Northwest Bio’s DCVax®-L Product
Northwest Biotherapeutics, Inc. announced that its partner in Germany, Fraunhofer IZI, has received the official approval and certification from the regional and national regulatory agencies in Germany for the manufacture of Northwest Bio’s DCVax®-L immune therapy for human patients with Glioblastoma multiforme brain cancer. [Northwest Biotherapeutics, Inc.] Press Release

Researchers Study Vaccine Created from Patient Blood Cells as Potential Weapon against Aggressive Brain Tumors
Researchers are seeking to understand if a vaccine made from a patient’s own blood cells may slow the growth of a type of brain tumor. The trial is studying the vaccine’s effect on glioblastoma multiformes, the most common and aggressive type of primary brain tumor. [Northwestern Brain Tumor Institute]
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NEW 11th Cancer Immunotherapy (CIMT) Annual Meeting
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