Reviews & Analysis

Signalling by pattern-recognition receptors (PRRs) is finely tuned by many regulators and amplifiers, and a complex interplay between PRR pathways and other immune receptor pathways helps to ensure that appropriate immune defence pathways are initiated and coordinated. Xuetao Cao describes some of the latest advances in this complex regulation.

In this Review, the authors relate the growing appreciation of the neuroimmune circuits that link inflammatory and immune responses with depressive behaviours. They explore the evolutionary basis of this neuroimmune link and discuss how a better understanding of these pathways may lead to new therapies that treat depression by targeting the immune system.

Here, the authors detail our current understanding of specialized pro-resolving mediators (SPMs), a family of endogenous mediators that have important roles in promoting the resolution of inflammation. With a focus on the lungs, they discuss the contribution of SPMs to infectious and chronic inflammatory diseases and their emerging therapeutic potential.

In this Review, the authors detail the emerging evidence that supports the existence of memory populations of regulatory T (T_Reg) cells. They explain the immunological settings in which memory T_Regcells develop, discuss the physiological relevance of these cells and address some of the key questions that remain for this rapidly evolving field.

The recent discovery that some memory T cells can become tissue resident after infection warrants further study into the mechanisms and therapeutic implications of such enhanced regional immunity.

Accumulating data are highlighting new roles for the caspase family of cysteine proteases beyond their well-established functions in apoptosis and inflammation. This Review describes these emerging roles for caspases in mediating distinct forms of programmed cell death and directing inflammasome and innate immune responses.

Activation of STING (stimulator of interferon genes) by cytosolic aberrant DNA species or cyclic dinucleotides triggers transcription of numerous innate immune genes. In this Review, the author summarizes recent insights into the regulation of STING signalling and its role in autoinflammatory disease and cancer.

This Review describes the role of the immune system in dengue pathogenesis. The authors also discuss new insights gained from human monoclonal antibodies against dengue virus as well as the recent vaccine trials and the challenges to develop an effective dengue vaccine.

Macrophages populate the body's tissues and organs, where they become highly specialized to preserve organ integrity in the event of microbial invasion or injury. A dynamic crosstalk between the macrophages and their surrounding tissue cells is crucial to ensuring this homeostatic function. This Review highlights the key molecules and mechanisms involved in macrophage–tissue interactions.

This Opinion article proposes that interleukin-15 (IL-15) is a master regulator of tissue-specific T cell responses to promote the destruction of infected cells. Hence, dysregulation of IL-15 production in tissues during sterile inflammation can lead to T cell-mediated autoimmunity.

Emerging evidence suggests that the stroma of the tumour microenvironment can shape antitumour immunity and responsiveness to immunotherapy. The stromal cells and the signals they produce that influence tumour-infiltrating leukocytes, as well as the implications for cancer treatment, are reviewed here.

Reciprocal interactions between leukocytes and endothelial cells enable leukocytes to recognize the blood vessel endothelium in areas of inflammation and transmigrate across the endothelial barrier to mount an immune response in infected and/or damaged tissues.

Here, the authors explain how the specificity and magnitude of the primary cytotoxic T lymphocyte (CTL) response is determined during a viral infection. They discuss the different factors that influence the recruitment and expansion of naive CTL precursors, and they explain how technological advances have enabled a more accurate quantitation of these responses.

γδ T cells have unique specificities, high clonal frequencies and a pre-activated differentiation status that allow rapid and non-redundant responses to tumours. Here, the authors review their often contrasting roles in cancer and the opportunities for γδ T cell-based cancer therapies.

The rapid response of innate immune cells requires metabolic reprogramming to support their specific effector functions. As discussed here, mTOR is a key regulator of this process: it senses the environmental and intracellular nutritional status of innate immune cells to dictate and optimize the inflammatory response.

This Review describes our current understanding of innate and adaptive immune responses in the urinary tract and how immunomodulatory therapies could provide benefit in an era of increasing antibiotic resistance among uropathogens.

This Review focuses on the lesser studied antigen-presenting molecules group 1 CD1 proteins and MHC class I-related protein (MR1). The authors explain how their mode of presentation of lipids and small molecules to T cells differs from that of peptide–MHC presentation, and how new technologies are revealing unique T cell subsets that are specific for CD1 and MR1 proteins.

This Review describes the host immune response toCandida fungal infections. The authors detail the innate and adaptive immune mechanisms, as well as the non-immune mechanisms, that are involved in the antifungal response. They also discuss emerging evidence suggesting that both innate and adaptive immune cells contribute to immune memory against Candidaspecies.

Here, the authors review new insights into the diverse and pleiotropic roles of cytokines at different stages of colorectal cancer development and progression, emphasizing mutations and epigenetic adaptations that influence the oncogenic potential of cytokines and summarizing the challenges posed by complex cytokine networks for cancer immunomodulatory therapy.

Nucleic acid-sensing receptors are crucial for initiating protective immune responses against viruses, but aberrant activation of these receptors can also drive pathological inflammation. In this Review, the authors discuss the new agonists and antagonists that are being developed to target these receptors in the clinic.