Volume 24 Issue 11, November 2023

Severe COVID-19 is marked by excessive inflammation that can persist after infection. The commensal yeast Candida albicans is now implicated in the acute and chronic immunopathology of COVID-19.

Immune checkpoint inhibitors provide beneficial anti-tumor immunity but risk immune-related adverse events occurring in normal tissues. Notably, selective deletion of PGLYRP1, a protein expressed by several immune cells, protects against tumor cell growth and autoimmunity.

Hogan et al. identify a co-immunodominant influenza peptide presented in mice by MHC-E, a nonclassical class I molecule. Notably, the peptide derives from a 16-residue alternative reading frame translated by leaky ribosome scanning of the M1 mRNA and is recognized by conventional CD8⁺ T cells.

Two new studies in which apoE expression in mice is manipulated provide insights into the roles of microglial apoE in neurodegeneration.

For decades, beta-blockers have been used widely to treat cardiovascular diseases. Surprisingly, new data show how these inhibitors can also improve immunotherapy against tumors and chronic infections.

The first conference on ‘Infection and Immunity’ was organized by the Institute for Basic Science and Korean Association of Immunologists and held in Daejeon, South Korea, from 12 to 14 July 2023. The conference focused on the biology of CD8⁺ T cells in the context of viral disease and cancer.

Genetic and environmental diversity are major drivers of macrophage transcriptional responses, but the mechanisms that underlie the relative contributions of gene-by-environment interactions to transcriptional responses of tissue macrophages are unclear. We defined the relative effect of cis regulation, cell-autonomous trans regulation, and non-cell-autonomous trans regulation of Kupffer cell gene expression.

A trimodal single-cell assay reveals a previously unknown T cell subset and cellular state differences between children and older adults that might contribute to age-specific immunity.

Kupffer cells, hepatic resident macrophages, are the first line of defense against liver metastases by engulfing disseminated malignant cells. We found that ERMAP expressed on tumor cells binds to galectin-9 and dectin-2 on Kupffer cells to deliver pro-phagocytosis ‘eat me’ signals to Kupffer cells to restrict liver metastases.

Santosa and Sun draw parallels from T cell biology to explore the key features of immune memory in innate lymphocytes.

Yuan and colleagues show that ERMAP expression on cancer cells delivers an ‘eat me’ signal to Kupffer cells by binding to Gal-9–dectin-2 on Kupffer cells and triggering phagocytosis.

The mechanisms by which noncoding genetic variation shapes tissue macrophage phenotypic diversity remain obscure. Glass and colleagues define cell-intrinsic and environmental effects contributing to genetic control of Kupffer cell transcription.

The APOE4 allele is a major genetic risk factor for the development of late-onset Alzheimer’s disease (AD). In this manuscript, Butovsky and colleagues suggest that APOE4 impairs the microglial response in AD by inducing TGFβ-mediated checkpoints.

Liu and colleagues find differential effects of microglial apoE isoforms on brain function and microglial responses. ApoE3 enhances microglial responses, promoting brain function and reducing amyloid deposition and associated neurotoxicity, while the Alzheimer’s disease-associated apoE4 results in lipid droplet accumulation and impaired microglial responses, which are critical for limiting the development of amyloid pathology.

Peduto and colleagues report a role for ADAM12⁺ mesenchymal stromal cells at the tumor margins and their interaction with immune cells to promote a permissive ‘protumor’ environment.

Iliev et al. report that increased Candida albicans accumulation in the mycobiota of patients with severe COVID-19 might be a contributing factor to the immunopathology of severe COVID-19 and have long-lasting effects on the hematopoietic stem cell compartment.

Here the authors use single cell profiling of T cells across the human lifespan to show that a suboptimal TCR shift in T cells as we enter older age results in a molecular signature that resembles that of T cells from newborns and children.

Here, the authors show that deletion of Pglyrp1 promotes antitumor immunity owing to its inhibitory function in CD8⁺ T cells and that targeting it can inhibit development of autoimmune neuroinflammation. These findings indicate that PGLYRP1 might be a target for immunotherapy.

The malate shuttle is understood to control the NAD⁺/NADH balance. Here the authors show that GOT1, a central enzyme in the malate shuttle, rather promotes antiviral CD8⁺ T cell responses by detoxifying ammonia.

Eisenlohr and colleagues identify a novel influenza A virus peptide that elicits a robust CD8⁺ T cell response and is restricted by the nonclassical Qa-1 class I molecule.

Using TEA-seq, Thomson et al. detail transcriptional and epigenetic alterations in the T cell compartment between healthy children and older adults, leading to the discovery of a novel pediatric CD8αα⁺ population poised for rapid effector responses.