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Reactive oxygen species (ROS) are generated by cells during viral infection. Pichlmair and colleagues demonstrate a ROS-dependent form of cell death, ‘oxeiptosis’, that resembles apoptosis but uses a pathway distinct from all previously described death pathways.
Plasmacytoid dendritic cells (pDCs) are known for their copious IFN-I production. Soumelis and colleagues show that functionally and transcriptomically distinct human pDC populations can be generated from a single microbial or cytokine stimulus.
RIG-I is a cytosolic RNA sensor. Gack and colleagues show that herpesviruses, duplex DNA viruses, also activate RIG-I by inducing cytoplasmic translocation and unmasking of an endogenous host 5S ribosomal pseudogene RNA, RNA5SP141.
Host cells display ‘don’t eat me’ signals to protect themselves from phagocytosis. Maute and colleagues identify a novel ‘don’t eat me’ system based on recognition of MHC class I by the phagocyte-expressed inhibitory molecule LILRB1.
Cao and colleagues identify the E3 ubiquitin ligase RNF2 as an inhibitor of interferon-dependent antiviral responses that acts by promoting the K33-linked polyubiquitination of STAT1 and its disassociation from DNA.
The survival of hematopoietic stem cells requires tight regulation of mitophagy. Lin and colleagues show that Atad3a regulates mitophagy in these cells by sequestering the mitophagy initiator Pink1 and directing its import via the mitochondrial Tom40–Tim23 complex.
The tumor microenvironment represents a stressful cellular environment. Zou and colleagues show that Treg cells in tumors have heightened sensitivity to apoptosis, but unexpectedly this increases their suppressive potency.
The polarization of leukocytes toward chemoattractants is essential for their directed migration. Chen and colleagues show that the phosphoinositide-transfer protein TIPE2 functions as a coordinator of leukocyte polarity.
Fagarasan and colleagues show that excessive activation of T cells in mice deficient in the inhibitory receptor PD-1 causes a systemic decrease in tryptophan and tyrosine, which leads to deficiency in serotonin and dopamine in the brain and behavioral changes.
Gillet and colleagues find that infection with a gammaherpesvirus confers strong and lasting protection against airway allergy through the replacement of lung-resident alveolar macrophages with recruited regulatory monocytes of bone marrow origin.
Type 1 diabetes has a multifactorial etiology. Lehuen and colleagues demonstrate that MAIT cells serve both positive roles and negative roles in type 1 diabetes by maintaining gut integrity and limiting pancreatic inflammation but also directly destroying β-cells.
NLR proteins contribute to antiviral immune responses. Lemon and colleagues show that NLRX1 promotes antiviral responses in hepatocytes by competing with the kinase PKR for viral double-stranded RNA, which allows accumulation of the transcription factor IRF1 for early control of viral replication.
T cells developing in the thymus are signaled during positive selection to differentiate into either CD4+ T cells or CD8+ T cells. Singer and colleagues show that CD8+-lineage specification is signaled exclusively by cytokines, including cytokines that do not signal via the γc receptor, and that these are the only signals in the thymus that upregulate the transcription factor Runx3d to direct specification to the CD8+ lineage.
Diamond, Screaton and colleagues show that certain cross-reactive neutralizing antibodies to dengue virus have therapeutic activity against Zika virus infection in immune-privileged sites in vivo.
Cross-reactivity to dengue virus serotypes can trigger life-threatening inflammation. Culshaw et al. show that germline-encoded components of dengue-virus-specific TCRs influence antigen engagament and suggest that ‘innate-like’ recognition of the virus might underpin harmful cross-reactivity.
NK cells are cytotoxic cells that combat tumors and viral infection. Finlay and colleagues show that the effector function of cytokine-activated NK cells depends on glucose metabolism via the citrate–malate shuttle that requires the metabolic regulator Srebp.
Foxp3 is the Treg cell lineage–defining transcription factor, but its mechanisms of action are still being elucidated. Benoist and colleagues comprehensively generate Foxp3 mutants to delineate how it functions in a cell-context- and molecular-complex-dependent manner.
Humoral immunity is necessary for controlling viral infection. Ballesteros-Tato and colleagues show that development of follicular regulatory T cells is prevented by high concentrations of interleukin 2 at the peak of viral infection, but resumes at later time points to suppress autoantibody production.
Ganss and colleagues show that targeting the inflammatory cytokine LIGHT to tumor vessels via a vascular targeting peptide induces tertiary lymphoid structures and enables the influx of endogenous T cells and tumor killing.