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Vitamin A deficiency exacerbates invasive non-typhoidal Salmonella infection in mice, revealing a restrictive role for SLC11A1 in neutrophils.

Bacterial ligands cannot induce Toll-like receptor 2 (TLR2)-dependent production of type I interferon. Barton and colleagues find that, in contrast, viral ligands trigger TLR2-dependent interferon production by a subset of inflammatory monocytes.

A diverse, multidisciplinary panel of 386 experts in COVID-19 response from 112 countries provides health and social policy actions to address inadequacies in the pandemic response and help to bring this public health threat to an end.

The interaction of UNC93B1 with syntenin-1 facilitates the sorting of TLR7–UNC93B1 complexes into intraluminal vesicles of multivesicular bodies, and mutations in UNC93B1 that disrupt such interactions lead to enhanced TLR7 signalling and autoimmunity.

The Toll-like receptor TLR9 is activated only after regulated release from its trafficking chaperone UNC93B1, which occurs within endosomes and is required for ligand binding and signal transduction.

An analysis of 24,202 critical cases of COVID-19 identifies potentially druggable targets in inflammatory signalling (JAK1), monocyte–macrophage activation and endothelial permeability (PDE4A), immunometabolism (SLC2A5 and AK5), and host factors required for viral entry and replication (TMPRSS2 and RAB2A).

The authors have previously demonstrated the neutralising capacity of their nanoparticle vaccine, as well as showing protection of non-human primates from SARS-CoV-2 WA-1 infection. In this work, they investigate the ability of their vaccine candidate to neutralise SARS-CoV-2 variants of concern, and protect animals from other sarbecoviruses.

Transposon mutagenesis identifies Akkermansia muciniphila genes required for growth on mucin and colonization of the intestinal tract.

Immunization of macaques with nanoparticle-conjugated receptor-binding domain of SARS-CoV-2 adjuvanted with 3M-052 and alum results in cross-neutralizing antibodies against bat coronaviruses, SARS-CoV and SARS-CoV-2 variants, and may provide a platform for developing pan-coronavirus vaccines.

Dimethyl fumarate (DMF) is an anti-inflammatory drug proposed as a treatment for COVID19. Here the results are reported from a randomised trial testing DMF treatment in 713 patients hospitalised with COVID-19. DMF was not associated with any improvement in day 5 outcomes.

Genetic and testing data from England show that the SARS-CoV-2 variant of concern B.1.1.7 has a transmission advantage over other lineages.

Sera from vaccinated individuals and some monoclonal antibodies show a modest reduction in neutralizing activity against the B.1.1.7 variant of SARS-CoV-2; but the E484K substitution leads to a considerable loss of neutralizing activity.

Chronic infection with SARS-CoV-2 leads to the emergence of viral variants that show reduced susceptibility to neutralizing antibodies in an immunosuppressed individual treated with convalescent plasma.

Post-international travel quarantine has been widely implemented to mitigate SARS-CoV-2 transmission, but the impacts of such policies are unclear. Here, the authors used linked genomic and contact tracing data to assess the impacts of a 14-day quarantine on return to England in summer 2020.

In this study, Aggarwal and colleagues perform prospective sequencing of SARS-CoV-2 isolates derived from asymptomatic student screening and symptomatic testing of students and staff at the University of Cambridge. They identify important factors that contributed to within university transmission and onward spread into the wider community.

Temporal multi-omic analysis of tissues from rats undergoing up to eight weeks of endurance exercise training reveals widespread shared, tissue-specific and sex-specific changes, including immune, metabolic, stress response and mitochondrial pathways.

The Omicron variant evades vaccine-induced neutralization but also fails to form syncytia, shows reduced replication in human lung cells and preferentially uses a TMPRSS2-independent cell entry pathway, which may contribute to enhanced replication in cells of the upper airway. Altered fusion and cell entry characteristics are linked to distinct regions of the Omicron spike protein.

A study of the evolution of the SARS-CoV-2 virus in England between September 2020 and June 2021 finds that interventions capable of containing previous variants were insufficient to stop the more transmissible Alpha and Delta variants.

A critical aspect of innate immune function is the coordinated regulation of inflammatory gene expression. Now an unexpected discovery shows that certain signaling components of the unfolded protein response are required for optimal gene induction by Toll-like receptors.

The activation and signalling pathways engaged by Toll-like receptors (TLRs) are determined by their localization in the cell. Here, the authors explain how generic cellular machinery involved in the compartmentalization of receptors and signalling molecules contributes to TLR function and regulation.

In Alzheimer’s disease (AD) tau and neurodegeneration have complex regional relationships. Here, the authors show neuronal hypometabolism discordant with tau burden defines functional resilience or susceptibility to Alzheimer’s pathology via limbic/cortical axes. Susceptible groups have faster cognitive decline and evidence of non-Alzheimer’s pathologies.

The identification of antibodies targeting a conserved site of vulnerability in the Plasmodium falciparum circumsporozoite protein reveals opportunities for passive prevention of malaria in vulnerable individuals and provides insights for rational vaccine design.

Toll-like receptors (TLRs) use multiple downstream signaling pathways. New data suggest that components of the tumor necrosis factor receptor signaling pathway are involved in signal transduction by certain TLR family members.

It is known that exercise influences many human traits, but not which tissues and genes are most important. This study connects transcriptome data collected across 15 tissues during exercise training in rats as part of the Molecular Transducers of Physical Activity Consortium with human data to identify traits with similar tissue specific gene expression signatures to exercise.

A genome-wide association meta-analysis study here shows novel genetic loci to be associated to body fat percentage, and describes cross-phenotype association that further demonstrate a close relationship between adiposity and cardiovascular disease risk.

Longitudinal sampling is used to map the evolution of an HIV-1 virus from the time of infection, and the co-evolution of a broadly neutralizing antibody in the same infected patient; the findings have important implications for HIV vaccine development.

Endolysosomal proteolytric cleavage is shown to be required for TLR9 activation by CpG

The SARS-CoV-2 spike ectodomain is destabilized by cold temperature storage, an effect that can be reversed by incubation at 37 °C or by stabilizing its conformation in the ‘down’ state.