Reviews & Analysis

Guanylate-binding proteins (GBPs) promote immune defenses against infectious agents. Two studies reveal that GBP1 directly binds to cytosolic lipopolysaccharide (LPS), bringing caspase-4 to the surface of bacteria to induce pyroptosis.

Antigen escape by solid tumors has limited the efficacy of genetically modified T cells. T cells engineered to secrete the cytokine Flt3L induce the activation of endogenous T cells, enabling a broader repertoire of tumor antigens to be targeted via the expansion of intratumoral antigen presenting cells, significantly improving tumor responses.

CAR T cells are engineered to recognize tumor-specific antigens and kill tumor cells. A study of CAR T cell activation using single-molecule microscopy reveals that CARs fail to efficiently convert antigen binding into early T cell signaling events.

Quantitative systems-level proteomics is cleverly used to reveal a dynamic program of protein turnover in naive and memory CD4⁺ T cells that, alongside a stockpile of metabolic protein machinery, poises the cells for activation.

Evolutionary genetic and experimental analyses suggest that mutations causing familial Mediterranean fever have been positively selected in the Middle East, probably because they confer heightened resistance against Yersinia pestis infection.

CXCR3⁺ regulatory T cells, known to limit type 1 immune responses, can promote tissue-resident immunity by providing bioactive transforming growth factor-β to CD8⁺ T cells.

Early plasmablasts responding to Plasmodium infection may outcompete germinal center B cells for l-glutamine and delay pathogen control.

Caspase-cleaved gasdermin D forms pores in cellular membranes, thus executing proinflammatory cell death by pyroptosis. Disulfiram — a drug used to treat chronic alcoholism — is now found to be an inhibitor of pore formation, which may therapeutically counteract exacerbated inflammation in sepsis and beyond.

The identification of the acute phase protein serum amyloid A as a soluble allergen sensor sheds new light on the mechanisms involved in the induction of type II airway inflammation.

A new report finds that peripheral immunization generates tissue-resident memory CD8⁺ T cells in the central nervous system that provide robust protection against local infection.

Host cell cholesterol is often exploited by pathogens for entry and egress. Two new studies elucidate a new interferon-inducible mechanism by which cells limit plasma membrane cholesterol to promote antibacterial defense.

B cells undergo iterative rounds of somatic hypermutation and selection for high-affinity antigen binding in the germinal center microenvironment. Two new studies provide insights into the temporal and spatial control mechanisms that act within B cells and follicular dendritic cells to jointly govern B cell differentiation and cell traffic within the GC.

A new study reports that T_H2-coordinated tissue repair takes precedence over long-term protective immunity in urinary tract infections. Although effective in the interim, this can lead to recurrent infections and bladder dysfunction.

Injury or infection renders patients vulnerable to secondary pneumonia. A new study indicates that SIRP-α triggers prolonged impairment of the phagocytic capacity of alveolar macrophages after the resolution of primary bacterial or viral pneumonia.

Myeloid-derived suppressor cells (MDSCs) occupy sites of chronic inflammation and suppress CD8⁺ T cell function. A new study describes the transfer of the metabolite methylglyoxal (MG) to T cells, which mediates this immunosuppressive mechanism.

Single-cell RNA-sequencing of myeloid cells during neuroinflammation identifies a new population of pathogenic Cxcl10-expressing phagocytes, which develop independently of Ly6C^hi monocytes but derive from early myeloid precursors shaped by the inflamed tissue microenvironment.

Activation of TLR–TRAF6 signaling by chronic inflammation in myelodysplastic syndromes increases the competitive advantage of HSPCs harboring MDS mutations through the upregulation of the ubiquitin-modifying enzyme A20 and a switch from canonical to non-canonical NF-κB signaling.

Oxidative stress is an imbalance in the production of reactive oxygen species and the ability to remove or detoxify these molecules, which causes cellular damage. Leveraging novel sequencing methods and high-throughput screens leads to the discovery of possible new therapies.

CD8 memory–phenotype differentiation is a T cell antigen receptor–governed process that begins in Eomes⁺ thymic precursors and is subsequently completed in the periphery. These CD8-MP cells can infiltrate tumors, where they express PD-1.

Epigenetic modifications are associated with distinct stages of autoreactive CD8⁺ T cell differentiation. DNA methylation and chromatin changes guide the acquisition of a memory-like phenotype and sustain prolonged autoimmune effector responses.