Volume 16 Issue 5, May 2015

The mediobasal hypothalamus detects increased amounts of tumor necrosis factor during the early phases of inflammation and relays this information to cells of the adaptive immune system by mobilizing free fatty acids.

The methyltransferase Ezh2, an epigenetic regulator associated with tumor-cell metastasis, also methlyates the cytoplasmic integrin adaptor talin. This modification inhibits the binding of talin to F-actin, which enhances the migration and invasion of dendritic cells and neutrophils.

Guanylate-binding proteins (GBPs) induced by type I interferon signaling cause lysis of Francisella bacteria that have reached the host-cell cytosol. The liberated bacterial DNA is then sensed by the cytosolic AIM2 inflammasome, which activates caspase-1 and leads to pyroptotic cell death.

The cell-surface receptor TREML4 amplifies cellular responses to single-stranded RNA by regulating recruitment of the adaptor MyD88 to the receptor TLR7. Mice lacking TREML4 show impaired antiviral immunity but also reduced severity of lupus-like disease.

IL-6 has context-dependent pro- and anti-inflammatory properties and is now regarded as a prominent target for clinical intervention. Hunter and Jones discuss the effect of IL-6 on innate and adaptive immunity, and consider how the immunobiology of IL-6 may inform clinical decisions.

Cells closely monitor mitochondrial status. Liu and colleagues show that the kinase Jnk2 regulates mitophagy by inhibiting smARF. Loss of Jnk2 results in defective mitophagy and enhanced ROS generation during hypoxia, which leads to enhanced inflammasome activation.

The mechanisms that control activation of the AIM2 inflammasome by cytosolic bacteria are unclear. Kanneganti and colleagues demonstrate that a pathway involving the transcription factor IRF1 is required for the activation of AIM2.

How host cells induce the release of DNA from cytosolic bacteria is unclear. Broz and colleagues show that the guanylate-binding proteins GBP2 and GBP5 trigger bacteriolysis in infected host cells and thereby allow recognition by the sensor AIM2.

Mutations in the gene encoding the helicase senataxin have well established associations with the neurodegenerative disease ALS. Marazzi et al. show that senataxin can also attenuate virus-triggered responses by controlling RNA polymerase activity at genes encoding antiviral molecules.

Fine-tuning of TLR7 signaling modulates innate inflammatory responses. Means and colleagues identify the receptor TREML4 as an essential positive regulator of TLR7 signaling during antiviral responses and autoimmunity.

Ezh2 is a protein methylase that epigenetically modifies chromatin. Su and colleagues identify a cytoplasmic role for Ezh2 whereby it controls the extravasation of innate leukocytes through methylation of talin and thereby influences inflammatory responses in vivo.

Singer and colleagues show that let-7 microRNAs target Zbtb16 mRNA, which encodes the transcription factor PLZF, to modulate PLZF expression during the terminal differentiation of NKT cells into effector subsets.

Peripheral innate immunological signals can amplify adaptive immune responses. Cai and colleagues show that hypothalamicexposure to the cytokine TNF triggers a neural response that amplifies peripheral lymphocyte activation in the spleen and adipose tissues.

Mature naive B cells express membrane IgM and IgD B cell receptors. Jumaa and colleagues show that the hinge region of these regions confers differential responses to monovalent versus multivalent antigens and thereby influences B cell reactivity.