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In a mouse model, environmental immunostimulation in early life led to cross-reactive adaptive immune memory and reduced type II immune responses to allergens, indicating a mechanistic relationship between environmental antigen exposure and subsequent allergy.

Here the authors show that LC3-associated phagocytosis is initiated by various receptors, which enrich phosphatidylserine in the membrane domains proximal to the phagosome, recruiting Rubicon to the membrane for phagosome maturation.

Basophils act as effector cells in immunoglobulin E–mediated hypersensitivity responses. Artis, Nakanishi and Medzhitov and their colleagues report that basophils present antigen and induce T helper type 2 responses to helminths, allergens and immunoglobulin E immune complexes.

A combination of gnotobiotic mouse models, transcriptomics, circuit tracing and chemogenetic manipulations identifies neuronal circuits that integrate microbial signals in the gut with regulation of the sympathetic nervous system.

Kubes and colleagues describe the presence in females of estrogen-driven, innate antibodies against specific oligosaccharides in EPEC that are maternally transferrable to offspring in mice and humans.

A study using mouse models of food allergy shows that allergic sensitization drives antigen-specific avoidance behaviour mediated by immunoglobulin E antibodies and mast cells.

Calcium phosphate nanoparticles formed naturally in the intestine aid the transport of soluble molecules from the gut lumen to immune cells of the intestinal tissue, and contribute to the immune surveillance and homeostasis of the gut.

Myoblast fusion is essential for skeletal muscle development and regeneration. Here the authors show that MyD88 is upregulated during myogenesis and during muscle growth, signals via the NF-κB and Wnt pathways, and that its expression modulates myoblast fusion and myofiber size in mice.

Individuals with long COVID show marked biological changes in cortisol and immune factors relative to convalescent populations.

The growth of tumours is supported by tumour production of lactic acid, which polarizes tumour-associated macrophages to an M2 phenotype through a pathway dependent on hypoxia-inducible factor 1α.

Alerting the immune system to invading microorganisms is essential for effective immunity. Uric acid released by damaged cells is a danger signal that is able to notify immune cells of microbial attack.

A longitudinal analysis of immune responses in patients with moderate or severe COVID-19 identifies a maladapted immune response profile linked to severe disease.

In mice, commensal bacteria are shown to provide critical signals that limit bacterial trafficking to the mesenteric lymph nodes by immune cells, thus preventing the induction of mucosal immune responses.

Resting and activated T cell states are established by context-specific regulators and dynamic gene circuits.

Elevated circulating levels of GDF15 in pregnant women are associated with severe nausea and vomiting, and sensitivity to such symptoms during pregnancy is partly determined by prepregnancy levels of this hormone.

Macrophages can be polarized by in vitro culture stimuli into M1 or M2 cells, but microenvironments in vivo are more complex. Here the authors analyze cultured macrophages stimulated with a combination of M1 and M2 stimuli by single-cell RNA sequencing, machine learning, and single-cell secretion profiling to show a surprising level of heterogeneity of response.

Although the only signalling motif in the adaptor protein DAP12 is generally thought to transduce activating signals, DAP12 has recently been shown to have inhibitory effects. A model to explain how this might occur is proposed in this Opinion article.

A circuit in the amygdala uses thyrotropin-releasing hormone to suppress male mating when a female mouse is unhealthy.

Galectins are important for recognition of carbohydrate ligands during embryogenesis, development and immune regulation. In addition, recent work has shown that galectins also function as receptors for glycans expressed on the surface of potentially pathogenic microorganisms. In this Review, Gerardo Vasta discusses the roles of galectins in host immunity and how pathogens have evolved to evade or subvert galectin-mediated immune responses.

How Toll-like receptors respond to specific ligands and activate selective signalling pathways is not fully understood. This Perspective proposes a molecular mechanism, involving a series of protein conformational changes that are initiated by receptor dimerization, that might account for this specificity.

Obesity changes the characteristics of the immune response induced in a mouse model of atopic dermatitis, suggesting therapies that could be used against immune dysregulation in obesity.

Several unconventional T cell populations, including γδ T cells and regulatory T cells, are selected by recognition of self antigen in the thymus. Craft and colleagues add T_H-17 cells to the list of T cell subsets enriched by self-reactivity.

Post-translationally modified histones are recognized by effector proteins which contain specific binding modules; for example, the bromodomain-containing BET proteins bind acetylated lysine residues during gene activation. Here a synthetic small molecule is described that interferes with the binding of certain BET family members to acetylated histones. The compound inhibits activation of pro-inflammatory genes in macrophages and has activity in a mouse model of inflammatory disease.

Dendritic cells in mice lacking NLRP10 are defective in exiting inflamed tissue, leading to impaired adaptive immunity; this could have a profound impact on the approach to treating allergic and autoimmune diseases.

Excess free fatty acids (FFAs) are known to induce insulin resistance, and a role for TLR4 has been implicated in this process. But FFAs are believed to be incapable of binding TLR4 directly. In a new study, Samir Bhattacharya and colleagues show that fetuin-A acts as an intermediary in this process by bindings FFAs and presenting them to TLR4. These results suggest fetuin-A as a new target to treat insulin resistance and diabetes.

Human immunodeficiency virus (HIV) fails to induce interferon in the cells that it infects, but the underlying mechanisms are not known. These authors show that the virus can in fact activate the interferon pathway in dendritic cells when the usual block to infection is bypassed. Dendritic cell activation depends on the HIV-1 capsid/cyclophilin A interaction, which is known to have a role in HIV-1 infectivity.