Don't stop me now - p821

doi:10.1038/ni0808-821

Despite pessimism in the media surrounding the recent failure of the Merck HIV vaccine, researchers should applaud their achievements and step up to the challenges ahead.

Full Text - Don't stop me now | PDF (183 KB) - Don't stop me now

Reflecting on a quarter century of HIV research - pp823 - 826

Andrew E Armitage, Andrew J McMichael & Hal Drakesmith

doi:10.1038/ni0808-823

The AIDS pandemic is caused by human immunodeficiency virus, which was discovered at the Institut Pasteur in 1983. In May 2008, scientists met in Paris to discuss the progress and setbacks of 25 years of research in this field and to debate future directions.

Full Text - Reflecting on a quarter century of HIV research | PDF (642 KB) - Reflecting on a quarter century of HIV research

A 'fly-by' killing with a primordial cellular weapon - pp827 - 829

Herbert Virgin

doi:10.1038/ni0808-827

Autophagy has been suggested—on the basis of in vitro studies—to be involved in defense against bacterial challenge. A study in drosophila now shows the importance of autophagy in vivo and links a pattern recognition receptor to the autophagy pathway.

Full Text - A 'fly-by' killing with a primordial cellular weapon | PDF (567 KB) - A 'fly-by' killing with a primordial cellular weapon

See also: Article by Yano et al.

Cat and mouse - pp829 - 830

Julio C Delgado & Peter E Jensen

doi:10.1038/ni0808-829

New findings show that ERAAP, an endoplasmic reticulum aminopeptidase involved in antigen processing, helps mice survive encounters with a feline-derived parasite.

Full Text - Cat and mouse | PDF (434 KB) - Cat and mouse

See also: Article by Blanchard et al.

NLRs and the dangers of pollution and aging - pp831 - 833

Stephen B Willingham & Jenny P-Y Ting

doi:10.1038/ni0808-831

The production of inflammatory interleukin 1 after uptake of silica crystals and alum salt or amyloid- occurs by a process that involves lysosomal destabilization and release of cathepsin B that activates the NLRP3 inflammasome.

Full Text - NLRs and the dangers of pollution and aging | PDF (1,275 KB) - NLRs and the dangers of pollution and aging

See also: Article by Hornung et al. | Article by Halle et al.

Distinct functions for HS1 in chemosensory versus adhesive signaling - pp833 - 834

Peter Beemiller & Matthew F Krummel

doi:10.1038/ni0808-833

Host immunity requires cytotoxic lymphocytes that are able to move toward their targets but are also able to stop after identifying target cells and then establish stable cell-cell contact. A new study shows that separate phosphorylation sites in HS1, an actin cytoskeleton–remodeling factor, can regulate both processes.

Full Text - Distinct functions for HS1 in chemosensory versus adhesive signaling | PDF (892 KB) - Distinct functions for HS1 in chemosensory versus adhesive signaling

See also: Article by Butler et al.

Arrestin NK cell cytotoxicity - pp835 - 836

Yenan T Bryceson & Hans-Gustaf Ljunggren

doi:10.1038/ni0808-835

A key regulator of the balance of signals that activate effector mechanisms versus those that restrain them, -arrestin 2 mediates the inhibition of natural killer cell cytotoxicity.

Full Text - Arrestin NK cell cytotoxicity | PDF (336 KB) - Arrestin NK cell cytotoxicity

See also: Article by Yu et al.

Research Highlights - p837

doi:10.1038/ni0808-837

Full Text - Research Highlights | PDF (118 KB) - Research Highlights

MicroRNAs: new regulators of immune cell development and function - pp839 - 845

David Baltimore, Mark P Boldin, Ryan M O'Connell, Dinesh S Rao & Konstantin D Taganov

doi:10.1038/ni.f.209

Abstract - | Full Text - MicroRNAs: new regulators of immune cell development and function | PDF (560 KB) - MicroRNAs: new regulators of immune cell development and function

Silica crystals and aluminum salts activate the NALP3 inflammasome through phagosomal destabilization - pp847 - 856

Veit Hornung, Franz Bauernfeind, Annett Halle, Eivind O Samstad, Hajime Kono, Kenneth L Rock, Katherine A Fitzgerald & Eicke Latz

doi:10.1038/ni.1631

Activation of the NALP3 inflammasome induces interleukin 1 production and inflammation. Latz and colleagues show that silica uptake followed by lysosome disruption and cathepsin B release activates the NALP3 inflammasome.

Abstract - | Full Text - Silica crystals and aluminum salts activate the NALP3 inflammasome through phagosomal destabilization | PDF (687 KB) - Silica crystals and aluminum salts activate the NALP3 inflammasome through phagosomal destabilization | Supplementary information

See also: News and Views by Willingham & Ting | Article by Halle et al.

The NALP3 inflammasome is involved in the innate immune response to amyloid- - pp857 - 865

Annett Halle, Veit Hornung, Gabor C Petzold, Cameron R Stewart, Brian G Monks, Thomas Reinheckel, Katherine A Fitzgerald, Eicke Latz, Kathryn J Moore & Douglas T Golenbock

doi:10.1038/ni.1636

The events leading to the inflammation and tissue damage associated with Alzheimer's disease are unclear. Golenbock and colleagues now show that amyloid- activates the NALP3 inflammasome, which triggers the release of proinflammatory and neurotoxic factors.

Abstract - | Full Text - The NALP3 inflammasome is involved in the innate immune response to amyloid- | PDF (804 KB) - The NALP3 inflammasome is involved in the innate immune response to amyloid- | Supplementary information

See also: News and Views by Willingham & Ting | Article by Hornung et al.

Superoxide dismutase 1 regulates caspase-1 and endotoxic shock - pp866 - 872

Felix Meissner, Kaaweh Molawi & Arturo Zychlinsky

doi:10.1038/ni.1633

The enzyme superoxide dismutase 1 (SOD1) protects cells from superoxide toxicity. Zychlinsky and colleagues find that post-translational glutathionylation of caspase-1 by SOD1 triggers caspase-1 activation and subsequent interleukin 1 production.

Abstract - | Full Text - Superoxide dismutase 1 regulates caspase-1 and endotoxic shock | PDF (424 KB) - Superoxide dismutase 1 regulates caspase-1 and endotoxic shock | Supplementary information

Resolvin E1 regulates interleukin 23, interferon- and lipoxin A₄ to promote the resolution of allergic airway inflammation - pp873 - 879

Oliver Haworth, Manuela Cernadas, Rong Yang, Charles N Serhan & Bruce D Levy

doi:10.1038/ni.1627

The influence of the lipid mediator resolvin E1 on adaptive immune responses is unclear. Levy and colleagues show that it suppresses airway inflammation in part by decreasing the release of IL-23 and IL-6 from dendritic cells.

Abstract - | Full Text - Resolvin E1 regulates interleukin 23, interferon- and lipoxin A4 to promote the resolution of allergic airway inflammation | PDF (509 KB) - Resolvin E1 regulates interleukin 23, interferon- and lipoxin A4 to promote the resolution of allergic airway inflammation | Supplementary information

Nonmuscle myosin light-chain kinase mediates neutrophil transmigration in sepsis-induced lung inflammation by activating ₂ integrins - pp880 - 886

Jingsong Xu, Xiao-Pei Gao, Ramaswamy Ramchandran, You-Yang Zhao, Stephen M Vogel & Asrar B Malik

doi:10.1038/ni.1628

To kill pathogens, neutrophils must be able to transmigrate into tissues. Xu and colleagues show that the kinase MYLK, by phosphorylating Pyk2, is required for neutrophils to reach sites of infection.

Abstract - | Full Text - Nonmuscle myosin light-chain kinase mediates neutrophil transmigration in sepsis-induced lung inflammation by activating 2 integrins | PDF (414 KB) - Nonmuscle myosin light-chain kinase mediates neutrophil transmigration in sepsis-induced lung inflammation by activating 2 integrins | Supplementary information

Differently phosphorylated forms of the cortactin homolog HS1 mediate distinct functions in natural killer cells - pp887 - 897

Boyd Butler, Diana H Kastendieck & John A Cooper

doi:10.1038/ni.1630

Essential for antigen-driven T cell responses, the cortactin homolog HS1 may also influence natural killer cell biology. Butler and colleagues identify functions for cortactin in natural killer cell cytotoxicity, adhesion and chemotaxis.

Abstract - | Full Text - Differently phosphorylated forms of the cortactin homolog HS1 mediate distinct functions in natural killer cells | PDF (814 KB) - Differently phosphorylated forms of the cortactin homolog HS1 mediate distinct functions in natural killer cells | Supplementary information

See also: News and Views by Beemiller & Krummel

An essential function for -arrestin 2 in the inhibitory signaling of natural killer cells - pp898 - 907

Ming-Can Yu, Liu-Li Su, Lin Zou, Ye Liu, Na Wu, Ling Kong, Zi-Heng Zhuang, Lei Sun, Hai-Peng Liu, Jun-Hao Hu, Dangsheng Li, Jack L Strominger, Jing-Wu Zang, Gang Pei & Bao-Xue Ge

doi:10.1038/ni.1635

Inhibitory receptors antagonize natural killer cell cytotoxicity. Ge and colleagues show that the scaffold protein -arrestin 2 recruits the phosphatases SHP-1 and SHP-2 to the inhibitory receptor KIR2DL1 to enhance 'downstream' inhibitory signaling.

Abstract - | Full Text - An essential function for -arrestin 2 in the inhibitory signaling of natural killer cells | PDF (605 KB) - An essential function for -arrestin 2 in the inhibitory signaling of natural killer cells | Supplementary information

See also: News and Views by Bryceson & Ljunggren

Autophagic control of listeria through intracellular innate immune recognition in drosophila - pp908 - 916

Tamaki Yano, Shizuka Mita, Hiroko Ohmori, Yoshiteru Oshima, Yukari Fujimoto, Ryu Ueda, Haruhiko Takada, William E Goldman, Koichi Fukase, Neal Silverman, Tamotsu Yoshimori & Shoichiro Kurata

doi:10.1038/ni.1634

The importance of autophagy in host survival during intracellular bacteria infection remains unclear. Kurata and colleagues show that in drosophila, autophagy initiated by the pattern-recognition receptor PGRP-LE promotes survival after Listeria monocytogenes infection.

Abstract - | Full Text - Autophagic control of listeria through intracellular innate immune recognition in drosophila | PDF (607 KB) - Autophagic control of listeria through intracellular innate immune recognition in drosophila | Supplementary information

See also: News and Views by Virgin

Identification of regulatory functions for 4-1BB and 4-1BBL in myelopoiesis and the development of dendritic cells - pp917 - 926

Seung-Woo Lee, Yunji Park, Takanori So, Byoung S Kwon, Hilde Cheroutre, Robert S Mittler & Michael Croft

doi:10.1038/ni.1632

The TNF receptor 4-1BB functions as a costimulatory molecule in T cells. Croft and colleagues show that binding of 4-1BB to its ligand regulates the production of dendritic cells by inhibiting myelopoiesis.

Abstract - | Full Text - Identification of regulatory functions for 4-1BB and 4-1BBL in myelopoiesis and the development of dendritic cells | PDF (803 KB) - Identification of regulatory functions for 4-1BB and 4-1BBL in myelopoiesis and the development of dendritic cells | Supplementary information

Regulation of B cell fate commitment and immunoglobulin heavy-chain gene rearrangements by Ikaros - pp927 - 936

Damien Reynaud, Ignacio A Demarco, Karen L Reddy, Hilde Schjerven, Eric Bertolino, Zhengshan Chen, Stephen T Smale, Susan Winandy & Harinder Singh

doi:10.1038/ni.1626

The transcription factor Ikaros has many functions essential for hematopoiesis. Singh and colleagues show that Ikaros is required for RAG recombinase expression and regulation of V_H accessibility in developing B cells.

Abstract - | Full Text - Regulation of B cell fate commitment and immunoglobulin heavy-chain gene rearrangements by Ikaros | PDF (851 KB) - Regulation of B cell fate commitment and immunoglobulin heavy-chain gene rearrangements by Ikaros | Supplementary information

Immunodominant, protective response to the parasite Toxoplasma gondii requires antigen processing in the endoplasmic reticulum - pp937 - 944

Nicolas Blanchard, Federico Gonzalez, Marie Schaeffer, Nathalie T Joncker, Tiffany Cheng, Anjali J Shastri, Ellen A Robey & Nilabh Shastri

doi:10.1038/ni.1629

The Toxoplasma gondii peptides recognized by protective CD8⁺ T cells remain uncharacterized. Shastri and colleagues identify an immunodominant T. gondii peptide generated by a mechanism dependent on the endoplasmic reticulum aminopeptidase ERAAP.

Abstract - | Full Text - Immunodominant, protective response to the parasite Toxoplasma gondii requires antigen processing in the endoplasmic reticulum | PDF (605 KB) - Immunodominant, protective response to the parasite Toxoplasma gondii requires antigen processing in the endoplasmic reticulum | Supplementary information

See also: News and Views by Delgado & Jensen

Erratum: Structure of and influence of a tick complement inhibitor on human complement component 5 - p945

Folmer Fredslund, Nick S Laursen, Pietro Roversi, Lasse Jenner, Cristiano L P Oliveira, Jan S Pedersen, Miles A Nunn, Susan M Lea, Richard Discipio, Lars Sottrup-Jensen & Gregers R Andersen

doi:10.1038/ni0808-945

Full Text - Erratum: Structure of and influence of a tick complement inhibitor on human complement component 5 | PDF (68 KB) - Erratum: Structure of and influence of a tick complement inhibitor on human complement component 5