Reviews & Analysis

Vaccine trials against Mycobacterium tuberculosis (Mtb) are showing encouraging results. This Review discusses current Mtb vaccine design in the light of new insights into the immunology of tuberculosis infection.

Tuft cells captured the attention of immunologists with recent discoveries linking them to type 2 immunity in the small intestine. As described here, these rare secretory epithelial cells act as chemosensory sentinels that detect and relay responses through immune and neuronal cells.

This Review covers new insights into the immune roles of complement. The authors discuss the pathways that link complement signalling with homeostatic and pathological T cell responses and highlight how complement components act intracellularly to shape T cell responses.

The NLRP3 inflammasome mediates pro-inflammatory responses and pyroptotic cell death. Here, the authors describe the complex pathways controlling its activation and regulation and how it is being targeted to treat inflammatory diseases.

In this Review, Greg Lemke explains how macrophages are able to sense and respond to dead and dying cells. The author discusses the physiological implications of such macrophage activity.

This Review presents evidence that supports a role for the immune system in the pathogenesis of hypertension, including the immune cell subsets involved and the means by which these immune cells become activated throughout the course of the disease.

Here, Ho and Kupper detail how T cell responses are generated and maintained in skin. They discuss how the various subsets of skin-resident T cells — including memory and innate-like populations — contribute to inflammatory skin disorders.

John Harty and colleagues explain how different subsets of CD4⁺ T cells, CD8⁺ T cells and γδ T cells respond to the Plasmodium parasites that cause malaria. They discuss the major challenges that need to be overcome in order to harness T cell responses for malaria vaccines and therapies.

Some immune cells undergo processes that pose unique challenges to the 3D organization of their genomes. These include antigen receptor rearrangement, clonal expansion and the contortion of their nuclei. Here, Allan and colleagues discuss the latest insights into these processes from a structural genomics perspective.

This Review describes the diverse and dynamic chromatin modifications that ensure rapid and appropriate innate immune responses to infection. It also discusses how pathogens themselves modify host responses through epigenetic mechanisms to evade elimination.

B cells have many unique metabolic features. Markus Müschen highlights these in this Opinion article and proposes the concept of three key metabolic gatekeepers that protect against B cell-associated autoimmunity and lymphomas.

This Review considers the link between pain and the immune system. Nociceptors are directly activated by immune mediators and microbial products and, in turn, release neuropeptides that shape immune responses. These neuroimmune pathways can contribute to protective immunity from infections but also lead to chronic pain.

The intestinal microbiota profoundly shapes host physiology through its production of small molecules and metabolites. Here, Honda and colleagues discuss how these microbial products shape immune function. They further consider the potential of ‘mining’ the microbiota for new microbial and metabolite-based immunotherapies.

Here, the authors explore how the transcription factor T-bet shapes innate and adaptive immune responses during infection. They consider the evolutionary relationship between T-bet and the related transcription factor eomesodermin (EOMES) and explain how T-bet controls the development of effector and memory T cell populations that mediate protective immunity.

Developing universal influenza virus vaccines will require understanding how broad and long-lived antibody responses to natural infection with influenza A virus are generated, a topic that has benefited greatly from technologies that enable the analysis of single human B cells.

Emerging data indicate that neutrophils exist in several different ‘flavours’. Here, the authors outline potential underlying mechanisms for the presence of distinct neutrophil subsets in health and disease.

In this Review, Erika Pearce and colleagues detail the metabolic changes that occur in the tumour microenvironment, explaining how these shape immune cell function at these sites. They highlight the potential of targeting these metabolic pathways to treat patients with cancer

As in other immune cells, the metabolic pathways in natural killer (NK) cells must be configured to meet the demands of their effector functions. This Review describes the specific metabolic requirements for NK cell responses and how defects in NK cell metabolism may contribute to NK cell dysfunction in chronic disease.

Double-strand breaks in DNA generated during the normal assembly and diversification of lymphocyte antigen receptor genes or by genotoxic agents during infection activate DNA damage responses. Besides repairing damaged DNA, these responses trigger important signalling events that regulate immune cell development and function.

Recent advances in systems immunology are beginning to elucidate the quantitative rules that govern cytokine-mediated cell-to-cell communication. This Review describes how combining theoretical analysis with experimental validation can lead to a better understanding of cytokine-mediated communication between cells of the immune system.