Immune Regulation News Volume 4.33 | Aug 31 2012

Infection-Induced NETosis Is a Dynamic Process Involving Neutrophil Multitasking In Vivo
Neutrophil extracellular traps (NETs) are released as neutrophils die in vitro in a process requiring hours, leaving a temporal gap that invasive microbes may exploit. Neutrophils capable of migration and phagocytosis while undergoing NETosis have not been documented. During Gram-positive skin infections, researchers directly visualized live polymorphonuclear cells in vivo rapidly releasing NETs, which prevented systemic bacterial dissemination. [Nat Med] Abstract

Type I Interferon Induces Necroptosis in Macrophages during Infection with Salmonella enterica Serovar Typhimurium
Researchers observed that host survival after infection with S. Typhimurium was enhanced in the absence of type I interferon signaling, with improved survival of mice deficient in the receptor for type I interferons that was attributed to macrophages. [Nat Immunol] Abstract

Inflammatory Monocytes Activate Memory CD8⁺ T and Innate NK Lymphocytes Independent of Cognate Antigen during Microbial Pathogen Invasion
Researchers showed that Ly6C⁺CCR2⁺ inflammatory monocytes, a subset of monocytes, largely orchestrate memory CD8⁺ T and NK lymphocytes activation by differentiating into interleukin-18 (IL-18)- and IL-15-producing cells in an inflammasome and type I interferon-IRF3-dependent manner. [Immunity]
Abstract | Press Release

NKT Cell Adjuvant-Based Tumor Vaccine for Treatment of myc Oncogene-Driven Mouse B Cell Lymphoma
Researchers aimed to boost anti-tumor immunity in B cell lymphoma by developing a tumor cell vaccine incorporating α-galactosylceramide that targets the immune adjuvant properties of NKT cells. [Blood] Abstract

Antibodies and IL-3 Support Helminth-Induced Basophil Expansion
Data revealed a role for isotype-switched antibodies in promoting basophil expansion and effector function following helminth infection. [Proc Natl Acad Sci USA] Full Article

IRF4 Promotes Cutaneous Dendritic Cell Migration to Lymph Nodes during Homeostasis and Inflammation
Researchers report that, although dispensable for their development, IFN regulatory factor 4 (IRF4) is crucial for the CCR7-mediated migration of CD11b⁺ dermal dendritic cells, a predominant population in murine and human skin that plays a vital role in normal and pathogenic cutaneous immunity. [J Immunol] Abstract

MiR-146a and NF-kB1 Regulate Mast Cell Survival and T Lymphocyte Differentiation
Researchers identified a new molecular network that comprises specifically the NF-kB family member NF-kB1 (p50) and miR-146a, and showed that in mast cells it contributes to the regulation of cell homeostasis and survival, while in T lymphocytes it modulates T cell memory formation. [Mol Cell Biol] Abstract

Strong and Sustained Effector Function of Memory versus Naïve Derived T Cells upon T-Cell Receptor RNA Transfer: Implications for Cellular Therapy
Researchers report that memory rather than naïve derived T cells are the preferred subset for transient T-cell receptor expression by RNA electroporation, providing more efficient and sustained virus-specific CD4⁺ and CD8⁺ T-cell function. [Eur J Immunol] Abstract

Nitric Oxide Inhibits the Accumulation of CD4+CD44hiTbet+CD69lo T Cells in Mycobacterial Infection
The authors showed that the absence of nos2 results in increased accumulation of neutrophils and both CD4⁺ and CD8⁺ T cells within the M. avium-containing granuloma. Examination of the T-cell phenotype in M. avium-infected mice demonstrated that CD4⁺CD44^hi effector T cells expressing the Th1 transcriptional regulator T-bet (T-bet⁺) were specifically reduced by the presence of nitric oxide. [Eur J Immunol]
Abstract | Press Release

Soluble ST2 Protein Inhibits LPS Stimulation on Monocyte-Derived Dendritic Cells
The authors previously reported that soluble ST2 suppressed the signal transduction of lipopolysaccharide (LPS) and cytokine production in monocytic cells. To investigate whether or not this inhibitory effect occurs in dendritic cells, which are the key players in innate and adaptive immunity, human monocyte-derived dendritic cells were pre-treated with soluble ST2 protein before LPS stimulation. [Cell Mol Immunol] Abstract

NEW! REVIEWS
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Endogenous Modulators of Inflammatory Cell Recruitment
In this review, researchers propose that locally produced modulators of leukocyte recruitment may represent local homeostatic mechanisms that tissues and organs may have evolved for protection against the destructive potential of the immune system. [Trends Immunol] Abstract

Capture, Crawl, Cross: The T Cell Code to Breach the Bloodbrain Barriers
With a focus on multiple sclerosis and its animal models, this review summarizes the distinct molecular mechanisms required for immune cell migration across the different central nervous system barriers. [Trends Immunol] Abstract

Northwest Bio Receives Regulatory Approval to Proceed with Its Phase III Trial in the UK
Northwest Biotherapeutics announced that it has received approval from the Medicines and Healthcare Products Regulatory Agency of the United Kingdom (UK) for the Company’s 300-patient Phase III clinical trial of DCVax^®-L immune therapy for Glioblastoma multiforme brain cancer to proceed [Northwest Biotherapeutics, Inc.] Press Release

Teva Announces FDA Grants Approval for Tbo-filgrastim for the Treatment of Chemotherapy-Induced Neutropenia
Teva Pharmaceutical Industries Ltd. announced that the U.S. Food and Drug Administration (FDA) has granted approval for tbo-filgrastim, the first new granulocyte colony-stimulating factor (G-CSF) to be approved in the United States in more than 10 years. Tbo-filgrastim is a short-acting recombinant form of G-CSF, indicated to reduce the duration of severe neutropenia in patients with certain types of cancer who are receiving chemotherapy that affects the bone marrow. [Teva Pharmaceutical Industries, Ltd.] Press Release

AHF to Take a Leading Role in HIV/AIDS Research
AIDS Healthcare Foundation (AHF) is pleased to announce that respected AIDS researcher and physician Otto O. Yang, M.D., Professor and Associate Chief of Infectious Diseases at the David Geffen School of Medicine at UCLA, will serve as inaugural Scientific Director of the Institue for Immunotherapeutic Research, a new HIV/AIDS research institute sponsored by AHF that will focus on translating basic science immunology research into human clinical trials. [AIDS Healthcare Foundation] Press Release

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