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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.
The similarities and differences between trained immunity and other immune processes are the subject of intense interrogation. Therefore, a consensus on the definition of trained immunity in both in vitro and in vivo settings, as well as in experimental models and human subjects, is necessary for advancing this field of research. Here we aim to establish a common framework that describes the experimental standards for defining trained immunity.
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.
Comprehensive analysis of specific and cross-reactive SARS-CoV-2 epitopes reveals functional T cell responses against specific viral regions in essentially all convalescent individuals and a majority of unexposed donors, demonstrating that cross-reactive responses to COVID-19 are widespread.
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.
Anjana Rao describes the team effort to define the changes in chromatin accessibility in naive T cells during TH1 and TH2 cell differentiation after stimulation with TCR ligands and the appropriate cytokines. Her lab showed that differentiated TH1 and TH2 cells, which produce the cytokines IFN-γ and IL-4, respectively, displayed distinct patterns of DNase I hypersensitivity, histone acetylation and NFAT1 transcription factor binding around the Ifng and Il4 genes. This project turned them into a ‘real’ immunology lab!
The natural variability of CRELD1 expression identified in comprehensive data sets from healthy individuals helps predict and establish its role in regulating T cell homeostasis.