Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain
the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in
Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles
and JavaScript.
The mechanism by which ingested material accesses the cytosol for cross-presentation is unclear. Caetano Reis e Sousa and colleagues demonstrate that signaling via the lectin receptor DNGR-1 ruptures the phagosome and releases its contents to the cytosol for cross-presentation.
Andreakos and colleagues provide a longitudinal study comparing patients with COVID-19 to patients infected with influenza. They report a dysregulated interferon response whereby IFN-λ and type I IFN production were diminished and delayed in patients with COVID-19, exhibiting a response that is ‘untuned’ with other inflammatory cytokines.
Geisbert and colleagues report that African green monkeys infected with the SARS-CoV-2 virus develop disease symptoms that closely resemble those seen in infected humans, making this animal model a useful surrogate to investigate immune responses to coronavirus infection.
Stem cell–like memory (TSCM) CD8+ T cells are beneficial in antitumor responses, in part due to their ability to self-renew. Khleif and colleagues demonstrate that inhibition of the kinase MEK in CD8+ T cells favors induction of TSCM and superior antitumor responses.
Mantovani and colleagues report elevated circulating concentrations of the long pentraxin PTX3 in patients with severe COVID-19. Within this cohort, early detection of high PTX3 concentrations emerged as a strong predictor of decreased survival.
Within a human cohort, wide variation can occur with constitutively expressed proteins. Aschenbrenner and colleagues found that individuals with lower CRELD1 expression have decreased frequencies of naive CD4+ T cells. Mice with conditional Creld1 deficiency also exhibit a phenotype associated with immunological aging.
COVID-19 is often characterized by a hyperinflammatory syndrome. Wang and colleagues show that low levels of IgG fucosylation enhance interactions with activating Fcγ receptors, boosting the inflammatory cytokines associated with severe COVID-19.
Farber and colleagues report distinct antibody responses to SARS-CoV-2 in pediatric cohorts, including those who developed multisystem inflammatory syndrome (MIS-C), and adult COVID-19 cohorts.
T cell memory formation is often described as occurring during the chronic phases of infection. Buchholz and colleagues use the phenomenon of ‘memory inflation’ following cytomegalovirus infection to show that a tiny subset of self-renewing T cells branch off early from the bulk population to generate memory.
Segal and colleagues identify a neuroprotective immature-like neutrophil subset that participates in dectin-1-dependent axon repair and regeneration in the central nervous system.
Exploring transcriptional heterogeneity of cKit+Sca1+ HSPCs using single cell RNA-sequencing, Naik and colleagues identify a population termed ‘lymphoid primed progenitors’ as the earliest stage of lymphoid lineage commitment, marked by downregulation of the stem/myeloid transcription factor Dach1.
The identity of stem-cell memory progenitor cells has been unclear. Lugli and colleagues use high-dimensional approaches to identify two new progenitor populations of human T cells—one giving rise to a functional lineage, the other to an exhausted-like one.
CD4+ T cells are critical for effective responses to infection with the malaria parasite. Haque and colleagues use single-cell RNA sequencing and computational modeling to track T cell memory development during experimental Plasmodium infection of mice.
Sanz and colleagues examine B cell subsets in a cohort of patients with COVID-19. Severely ill patients have higher frequencies of activated extrafollicular T-bet+ B cells that form antibody-secreting cells, the majority of which express germline sequences and are reminiscent of antibody responses observed in patients with systemic lupus erythematosus during flares.
Sepsis is a biphasic disease characterized by an initial inflammatory phase, followed by a prolonged immunosuppression phase. Puthalakath and colleagues utilize a CRISPR-mediated mutagenesis screen to identify TREML4 as a regulator of sepsis-induced immunosuppression.
Humans with inherited defects in DOCK8 expression are prone to allergic, type 2 CD4+ T cell responses. Mandl and colleagues reveal an important role for cell death in driving such type 2 signals during infection.
Ho and colleagues report that mitochondrial dysfunction and impaired mitophagy triggered by the tumor microenvironment lead to subsequent epigenetic changes and cause permanent T cell exhaustion and dysfunction.
SARS-CoV-2-specific CD4+ and CD8+ T cell epitopes are found in both convalescent patients and virus-naive volunteers and are indicative of heterologous recognition shared with seasonal cold viruses.
The pathways controlling T follicular helper (TFH) cell development are only partially understood. Allen and colleagues demonstrate the importance of the T cell receptor, with low tonic signaling promoting TFH cell development and high tonic signaling opposing it.