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Analysis of the blood DNA virome in patients with COVID-19 and autoimmune disease associates endogenous HHV-6 (eHHV-6) and high anellovirus load with increased disease risk, most notably for systemic lupus erythematosus. eHHV-6 carriers show a distinct immune response.

A genome-wide association study highlights a variant in DOCK2, which is common in East Asian populations but rare in Europeans, as a host genetic risk factor for severe COVID-19.

In cancer it is assumed that microRNAs recognise and regulate their targets uniformly. Here, the authors show that in gastrointestinal cancers methylation of microRNAs may impact their stability, and that levels of microRNA methylation are distinct in pancreatic cancer patients compared to healthy controls with potential diagnostic implications.

A global network of researchers was formed to investigate the role of human genetics in SARS-CoV-2 infection and COVID-19 severity; this paper reports 13 genome-wide significant loci and potentially actionable mechanisms in response to infection.

Previous genome-wide association studies have identified risk loci for pancreatic cancer but were centered on individuals of European ancestry. Here the authors identify GP2 gene variants associated with pancreatic cancer susceptibility in populations of East Asian ancestry.

The hepatitis B vaccine is recognised as the most effective approach in reducing hepatitis-B-related morbidity; vaccine-escape mutations are however capable of infecting vaccinated individuals. In this work, authors aim to establish a hepatitis B vaccine candidate, which they assess in rhesus macaques in terms of efficacy and safety.

Peripheral blood mononuclear cells from 73 Japanese patients with coronavirus disease 2019 (COVID-19) and 75 healthy controls were analyzed using single-cell transcriptomics. Combining these data with genotyping data highlights the interplay between host genetics and the immune response in modulating disease severity.

Hunger modulates perception of good and bad tastes. Here, the authors report that orexigenic AgRP neurons in the hypothalamus mediate these effects through glutamatergic lateral hypothalamic neurons that send distinct projections to the lateral septum and lateral habenula.

Using more than 100 independent iPSC lines derived from patients with Alzheimer’s disease, the authors discovered loci associated with the neuronal production of amyloid β and confirmed their influence using RNA interference.

Autoimmune pulmonary alveolar proteinosis (aPAP) is a complex lung disease caused by abnormal surfactant homeostasis. Here, the authors carry out a genome-wide association study of aPAP in a Japanese cohort, finding variants in the MHC and suggesting predisposition to abnormal antibody production.

Antimicrobial resistance to currently available antibiotics requires innovation of antibiotics. Here, the authors identify a critical inhibitory site in an energy-producing enzyme, which can lead to rational design of antibiotics.

Antibody cross-reactivity can help to prevent escape mutations from enabling viral escape, but underlying mechanisms are unclear. Here the authors identify influenza hemagglutinin epitopes that are exposed during viral replication and which result in the generation of a class of protective cross-reactive antibodies.

How alum acts as a vaccine adjuvant continues to perplex. Here Marichal et al. now report that alum induces host cell death and release of genomic DNA, which acts as an endogenous damage-associated molecular pattern that stimulates antibody and T cell responses

The vomeronasal system regulates sensing of various environmental cues. Here, the authors show that exposure to hemoglobin results in the activation of Vmn2r88+ vomeronasal sensory neurons in both male and female mice. However, exposure to hemoglobin enhances digging and rearing behaviour in lactating female mice only.

It is unclear whether microbes can efficiently degrade biodegradable plastics in the extreme environmental conditions of the seafloor. Here, Omura et al. show that biodegradable plastics can be degraded by the action of microorganisms on the deep-sea floor, although with much less efficiency than in coastal settings.

Seishi Ogawa and colleagues report the results of a large-scale sequencing study of adult T cell leukemia/lymphoma. They find recurrent alterations enriched for T cell receptor/NF-κB signaling, T cell trafficking and other T cell pathways and highlight targets for the development of new therapeutics for this intractable cancer.

Selective autophagy helps to degrade aggregated proteins accumulating in neurodegenerative diseases. Here, the authors show that NEMO, a ubiquitin binding protein previously linked to innate immune signaling, is recruited to misfolded proteins and promotes their autophagic clearance by forming condensates with the autophagy receptor p62.

The synthesis of NPY and its receptor Y1R increases in lung phagocytes during severe influenza virus infection, leading to the induction of SOCS3 and impaired antiviral response and increased pro-inflammatory cytokine production.

Plant colonization of land is an important evolutionary event. Here, the authors sequence the genome of a filamentous terrestrial alga and, through a comparative analysis with related algae and land plant species, provide insight into how aquatic algae adapted to terrestrial environments.

Primary productivity in the oligotrophic ocean sustains Earth’s ecosystems, but nutrient concentrations are vanishingly low. Here the authors measure nanomolar macronutrient concentrations in the North Pacific and find that net community production is sustained through high rates of phosphorus recycling.

Personalized neoantigen vaccines offer the potential to boost immune response a patient against their specific cancer antigens. Here, Katsikis, Ishii and Schliehe discuss the challenges that currently limit this therapeutic approach, including those related to neoantigen selection and adjuvants, and post-vaccine challenges such as the immunosuppressive tumour microenvironment. Moreover, they consider solutions that could help to overcome these obstacles.

DNA vaccines induce adaptive immune responses mainly via induction of type-I interferon. This paper shows that this occurs by a mechanism that is independent of the activation of nucleic acid binding Toll-like receptors. B and CD4⁺ T cell responses require activation of the TBK pathway in hematopoietic cells, whereas TBK1 in non-hematopoietic cells is critical for the activation of CD8⁺ T cells.

Producing plant secondary metabolites by microbes is limited by the known enzymatic reactions. Here, the authors apply machine learning to predict missing link enzymes of benzylisoquinoline alkaloid (BIA) biosynthesis in Papaver somniferum, and validate the specialized activities through heterologous production.

Mice pre-treated with lipopolysaccharides and metal nanoparticles, 10 nm or smaller, can cause a CD4⁺ T-cell-dependent allergic response similar to metal allergy seen in humans, suggesting that metal nanoparticles could potentially be a new trigger for metal allergy.

Bioproduction of tetrahydropapaveroline (THP) is limited by the specificity of monoamine oxidase (MAO). Here, the authors identify an insect 3,4-dihydroxyphenylacetaldehyde synthase (DHPAAS) that can bypass MAO for direct aldehyde production and demonstrate bifunctional switching of DHPAAS for efficient THP production.

Ionizing radiation damages small intestinal crypt cells, including epithelial stem cells and their progeny. Here the authors show that radiation-induced crypt cell death is amplified by the release of cellular RNA from apoptotic epithelial cells, which then triggers pro-apoptotic TLR3 signalling on neighbouring cells.

How APCs encounter T cells in the periphery remains unclear. Kabashima and colleagues show that dendritic cells form macrophage-dependent clusters in dermal perivascular areas for efficient in situ proliferation and activation of T cells.

The characteristics of the cell type(s) responsible for initiating protective gut immune responses are not fully defined. Akira and colleagues show that TLR5⁺ lamina propria dendritic cells trigger, in a retinoic-dependent way, the production of interleukin 17 and immunoglobulin A.

Isolation and characterization of an archaeon that is most closely related to eukaryotes reveals insights into how eukaryotes may have evolved from prokaryotes.

Nucleic acids modulate T cell responses; however, the physiological significance of this property remains unclear. Here, the authors show that self-DNA complexes with antimicrobial peptides or histones, which mediates T cell costimulation to induce Th2 cell differentiation.

It is becoming increasingly clear that the activation of the innate immune system by host or microbial nucleic acids contributes to the immunogenicity of many vaccines. This article describes the receptors and signalling pathways that are involved in sensing nucleic acids and discusses the implications for current and future vaccination strategies.