Volume 9 Issue 8, August 2008

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.

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.

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

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

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.

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

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

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

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 1β production.

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.

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.

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.

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

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.

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.

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.

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.